Abstract
In recent years proteomic techniques have started to become very useful tools in a variety of model systems of developmental biology. Applications cover many different aspects of development, including the characterization of changes in the proteome during early embryonic stages. During early animal development the embryo becomes patterned through the temporally and spatially controlled activation of distinct sets of genes. Patterning information is then translated, from gastrulation onwards, into regional specific morphogenetic cell and tissue movements that give the embryo its characteristic shape. On the molecular level, patterning is the outcome of intercellular communication via signaling molecules and the local activation or repression of transcription factors. Genetic approaches have been used very successfully to elucidate the processes behind these events. Morphogenetic movements, on the other hand, have to be orchestrated through regional changes in the mechanical properties of cells. The molecular mechanisms that govern these changes have remained much more elusive, at least in part due to the fact that they are more under translational/posttranslational control than patterning events. However, recent studies indicate that proteomic approaches can provide the means to finally unravel the mechanisms that link patterning to the generation of embryonic form. To intensify research in this direction will require close collaboration between proteome scientists and developmental researchers. It is with this aim in mind that we first give an outline of the classical questions of patterning and morphogenesis. We then summarize the proteomic approaches that have been applied in developmental model systems and describe the pioneering studies that have been done to study morphogenesis. Finally we discuss current and future strategies that will allow characterizing the changes in the embryonic proteome and ultimately lead to a deeper understanding of the cellular mechanisms that govern the generation of embryonic form.
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Introduction
Embryogenesis, the formation of a complete organism from an undifferentiated egg, has fascinated observers since Aristotelian times and experimental approaches to unravel the mechanisms behind embryogenesis date as far back as the late 19th century [1]. Early embryologists used ablation and transplantation techniques to manipulate embryos and it was soon realized that developing embryos have a high capacity to self-regulate. This was first demonstrated by Hans Driesch, who, by separating the two first blastomeres of see urchin embryos, demonstrated that each blastomere has the capacity to form a complete, half-sized organism [2]. The work of Driesch and other embryologists found its culmination in the definition of the "organizer" by Spemann and Mangold. They showed that the transplantation of a small region from the dorsal side of an early gastrula embryo into the ventral side of a host embryo results in the formation of a Siamese twin with a complete secondary axis [3]. Both donor and host cells contributed to this secondary axis indicating that the transplant induced surrounding cells to change from ventral to more dorsal fate and to participate in the necessary movements to form an elongated axial structure. For the prove of embryonic induction Hans Spemann received the Nobel Prize of Medicine in 1935. The question of what constitutes such inducing signals in the embryo (patterning) and how they control cell behavior to form the shape of the embryo (morphogenesis) has remained at the core of developmental biology since these seminal experiments.
The molecular basis of patterning
During the early period of experimental embryology, fundamental concepts have been formulated despite the lack of any knowledge about the molecular basis of development. One of the most influential theories was certainly the proposal of morphogens as inducers of patterning [4, 5]. Morphogens are defined as factors that, diffusing from a local source, generate a gradient that determines the cell fate of surrounding tissues in a concentration-dependent manner. The search for the molecular basis of patterning received an enormous boost with the execution of the first large scale mutational screen for defects in early Drosophila development. This led for example to the molecular description of the first morphogen, Bicoid, a transcription factor that forms a concentration gradient in the anterior half of the syncytial fly embryo and defines different anterior structures [6, 7]. Many other model systems, like e.g. frog, nematode, zebrafish and mouse, have been explored since then and have contributed to our current understanding of patterning processes (e.g. [8–10]). Today we know that patterning and the fascinating ability of embryos to self-regulate and regenerate is based on a complex interplay between signaling pathways that relies mainly on secreted signaling molecules, their antagonists and the local activity of transcription factors [11]. The exponential increase in knowledge about the molecular basis of patterning is intimately linked to the rise of molecular biology. The development of efficient sequencing, in situ hybridization, RNAse protection and RT-PCR has allowed determining the spatial and temporal distribution of mRNA encoding relevant factors in the embryo and in isolated tissues. Molecular cloning has allowed for the generation of deletion constructs to define functionally relevant domains in proteins, for the design of dominant negative and constitutively active constructs and for the use of reporter constructs to study the activity of promoter regions. In addition, the discovery of RNAi and the development of new, modified antisense constructs have added new techniques to the molecular "tool box" that have become invaluable to study gene function [12, 13].
It appears now that in several species, including the "classic" model systems Drosophila melanogaster and Xenopus laevis, a reasonably "complete" list of genes that are involved in early pattern formation has emerged. This undertaking has become even more feasible in recent years, since the genomes of several model animals have been completely sequenced, including fruit fly, nematode and sea urchin, and other genomes are close to completion and/or large cDNA and EST databases have been built [14–19]. Therefore in several species the resources and the tools are available to characterize the spatial and temporal expression of every gene. The systematic characterization of expression patterns and regulatory interactions between patterning genes is well underway [15, 20–22], shifting the focus of this research now to the analysis of the regulatory networks that are formed by these genes [23, 24] and the mathematical modeling of patterning events in early embryos [25]. Taken together, during the last thirty years embryology has made huge strides to elucidate the molecular basis of pattern formation and thereby to answer questions of embryology that have been raised a century ago. However, it has also become evident that the systematic approaches (e.g. mutagenesis, overexpression and knock down screens) used so successfully to study pattern formation are not sufficient to resolve questions of morphogenesis in a similar manner.
The molecular basis of morphogenetic movements
To study morphogenesis essentially means to ask how cells and tissues translate the positional information they have received into regional specific cell behaviors to give the embryo its defined shape. In animals, the first global cell rearrangements occur as gastrulation is initiated. Gastrulation is defined as the internalization of the prospective endoderm and mesoderm into the embryo and, while different species use different means and mechanisms to achieve internalization, the result is always the same: the endoderm forms the inner layer, the ectoderm remains on the outside and the mesoderm is located in between. After gastrulation, the three germ layers are in close apposition to each other; but they are clearly separated and mixing between the different layers rarely occurs, indicating that these cells can distinguish "similar" cells from "different" cells. This ability was demonstrated in dissociation and reaggregation experiments. Cells from early amphibian embryos can easily be separated by removal of calcium from the culture medium. Mixing of cells from the different germ layers and restoring of the calcium levels will lead first to a ball of mixed cells, but then cells will not only reaggregate according to their germ layer affiliation, but also assume the same position as in the embryo: ectoderm on the outside, mesoderm next and endoderm on the inside. These classical experiments led to the proposal of differential affinity between germ layer cells and later to the concept of differential adhesion to explain the ability of cells of different tissues to remain separate from each other [26–29]. One very important family of cell-cell adhesion molecules is constituted by transmembrane molecules of the cadherin family [30]. However, how their activity is differentially regulated between germ layers and later between developing tissues is to a large extent unclear. For example, C-cadherin is absolutely required for cell-cell adhesion in the early Xenopus embryo [31, 32] and its adhesive strength and dynamics are tightly regulated during gastrulation to facilitate cell movements and the separation of the germ layers. While some of the signals that change C-cadherin activity have been characterized in this context, it is still unknown how these changes are mediated on the mechanical level [33–36].
Likewise, our understanding of the molecular mechanisms that drive the cellular movements and cell shape changes during embryogenesis is still very fragmented. In several species gastrulation movements have been characterized in great detail and employed to develop general models of coordinated cell movements and shape generation [37–41]. These movements can often be correlated with the expression of certain patterning genes, but the downstream signals that regulate cell behavior and the means by which they modify mechanical attributes of cells are mostly unknown. The actin cytoskeleton for example is certainly involved in cell movements that require protrusive and contractile activity and the enormous progress that cell biologists have made in identifying the protein components that provide the basis of cytoarchitecture has sparked new interest in characterizing the role of these proteins in the embryo [42–45]. However, in general changes in the architecture, dynamics and contractility of the cytoskeleton appear to rely to a large extend on signaling, posttranslational modifications and differential use of a set of accessory proteins and much less on changes in gene expression [46–49]. Many cytoskeletal proteins have also essential functions in other processes like e.g. cell division and endo-exocytosis [50, 51], which might render it often very difficult, if not impossible, to interpret the effects of a broad interference with their activity. In addition, the control of translation and posttranslational modifications of proteins provide additional layers of regulation that might influence the abundance, splicing variants, subcellular localization and activity of a given protein in a cell. Nevertheless, progress has been made for example to bridge the gap between patterning signals and cell shape changes [52–54] or to elucidate the role of actin regulators [44, 55, 56] in specific morphogenetic movements. However, it appears that the molecular basis of cell behavior is difficult to decipher systematically by the means of molecular and genomic biology (e.g. mutational screens and gene expression analysis). Proteomic techniques provide in principle the right tools to directly characterize the changes in concentration, posttranslational modification and complex composition of sets of proteins during development and systematic proteomic approaches will hopefully allow to gain further insight into the molecular mechanisms that drive morphogenesis.
Analyzing developmental processes with proteomic tools
Proteomic approaches have already strongly contributed to many research areas in the medical sciences and in biology. Such areas include for example the study of cellular organelles [57–60] and protein interaction networks [61–63], certain aspects in cancer research [64, 65] and the study of synapses in neurobiology [66–68]. In recent years proteomic techniques have also become employed in several model systems of developmental biology, in a diverse array of contexts. A selection of reports on "developmental proteomics" is summarized in Table 1. Embryogenesis -in molecular terms- is reflected in the temporal and spatial changes of protein presence and activity. Several studies have been performed to compare levels and/or isoform shifts of proteins between different stages of development in zebrafish, Drosophila, mouse and chick [69–74] or to characterize protein differences between different embryonic tissues at the same point of development [75–77]. In almost all of these studies the proteome has been characterized using 2D-gel based protein separation and subsequent mass spectroscopy. This approach is relatively straight forward and allows detecting changes in protein quantities as well as shifts in isoform distribution directly on the gel. Apart from general characterizations of embryonic proteomes, 2D-gel approaches have also been used to detect protein differences after specific signaling events. One example is the comparison of egg proteins from sea urchin before and after fertilization. In this case the combination of protein and phospho-specific stains has allowed to identify several proteins that change in abundance and phosphorylation state within minutes after fertilization [78]. Another example is the characterization of protein differences after Thyroid hormone treatment in Rana tadpoles to study metamorphosis, which has, among other things, led to the identification of a novel larval keratin as a target of Thyroid-mediated signaling [79]. However, a 2D-gel approach has certain limitations: low abundance proteins might not be detected since the amount of sample that can be loaded on a 2D-gel is limited and the cellular concentration of proteins varies widely [80, 81]. Highly abundant proteins will also mask close by or overlapping weaker protein spots. In addition, certain types of proteins have properties (e.g. high hydrophobicity) that make them difficult or even impossible to be resolved in a 2D-gel approach. This can for example lead to an underrepresentation of integral membrane proteins [81, 82]. An alternative method is provided by "peptide-centric" proteomics, were the proteins in a given sample are digested first, yielding in general more soluble fragments, and the resulting peptide-mix is fractionated and analyzed by mass spectroscopy [83]. In a recent study in zebrafish embryos, both methods were employed in parallel. Interestingly, only about 30% of the characterized proteins appeared in both approaches, indicating that the two methods might rather complement each other [70]. In general, each approach to analyze an embryonic (or other organismal) proteome appears to yield only a subset of proteins at the present time. More complete inventories of an embryonic proteome at a given stage of development can certainly be obtained through a combination of different approaches, including initial subfractionation/enrichment steps to reduce the complexity of a sample before protein identification [84]. On the peptide side the complexity can be reduced by selection of a limited number of representative peptides to be analyzed per protein [85, 86]. On the protein side the sample can for example be fractionated according to protein size, by one-dimensional gel electrophoresis, before digestion [57]. Other fractionation techniques allow to separate proteins according to their spatial distribution in a cell (e.g. organelle fractions) or according to their posttranslational modifications (e.g. phosphorylation) [59, 87, 88]. Such approaches have been used already to isolate specific subpopulations of proteins from embryos. Several studies have been performed to biochemically isolate and then characterize phosphorylated proteins from Drosophila, mouse and zebrafish embryos [89–92]. The large phosphopeptide databases generated from such studies provide new insights into signaling pathways that are active during development. Other studies include for example the isolation of matrix vesicles during chick embryo bone formation [93]. These organelles are important mediators of bone mineralization. 126 organelle proteins were identified, several of which were previously unknown. In the nematode C.elegans biochemical purification of chondroitin proteoglycans and subsequent mass spectroscopy led to the characterization of 9 new proteoglycan core proteins with no apparent sequence homology to chondroitin proteoglycans in other species [94]. Simultaneous RNAi-based knock down of two of these proteins results in multinucleated single-cell embryos, indicating an essential role for chondroitin proteoglycans during cytokinesis. Results like these demonstrate how the combination of biochemistry to isolate a cellular organelle or protein subpopulations and mass spectroscopy can provide powerful tools to dissect developmental processes that would have been much more difficult if not impossible to analyse otherwise.
Proteomic approaches to study morphogenesis
During embryogenesis, discrete regions in the embryo display specific morphogenetic activities. The sum of these activities produces the final shape of the embryo. Regionalization of morphogenetic behavior poses an important challenge for the application of proteomic tools, mainly because sufficient amounts of a given tissue -that undergoes a specific movement- have to be obtained for subsequent analysis. Tissue formation and thereby the related cell behavior is under the control of upstream patterning signals and, to obtain large amounts of starting material, the manipulation of such signals has been employed to obtain mutant embryos that are either deficient or enriched in a certain tissue.
In Drosophila gastrulation begins with the internalization of mesodermal precursor cells on the ventral side of the embryo. This movement is initiated by shape changes of ventral cells that lead to the formation of a furrow. To study changes in the protein composition of ventral cells during this period of development the group of Jonathan Minden compared mutant embryos which are strongly ventralized to embryos where the ventral cells have adopted a lateral fate [76]. By difference gel electrophoresis (DIGE), they identified a total of 1315 protein spots, 105 of which showed differences in expression or isoform distribution. They were able to determine the identity of 65 differentially expressed protein spots, originating from 37 unique proteins [76]. The largest groups of isolated proteins were comprised by metabolic enzymes and proteases. However, in addition several cytoskeleton and membrane associated proteins were found to be differentially regulated, providing a starting point for a more detailed analysis.
A second study compared gastrulation stage zebrafish embryos that consisted mainly of cells of ectodermal respectively mesendodermal character [75]. In zebrafish, mesendoderm induction and the subsequent ingression of these cells during gastrulation depend on TGF-β-like Nodal signals. Suppression of this signal, in this study by using one-eyed-pinhead mutant embryos, produces "ectodermal" embryos [95], while overexpression of Nodal results in "mesendodermal" embryos [75, 96]. Using DIGE, 36 differentially expressed proteins were identified, including several cytoskeletal proteins. Among these proteins was Ezrin, a member of the ERM-family of proteins that links transmembrane proteins to the actin cytoskeleton [97]. The activity of these proteins is regulated by phosphorylation and closer analysis of Ezrin in the gastrulating zebrafish showed that it becomes preferentially phosphorylated in the mesendoderm. In addition, antisense-mediated knock down of Ezrin resulted in reduced cell migration of mesendodermal precursors during gastrulation, indicating that proper expression of Ezrin is important for these movements.
Another possibility is to interfere specifically with signals that have been found to be involved in the control of tissue movements and to identify thereby downstream signaling events. This approach has been used to study Fyn/Yes dependent signal transduction during zebrafish axis formation [91]. During vertebrate gastrulation, cells converge towards the dorsal midline, which leads to an elongation of the anterior-posterior axis and the formation of the characteristic elongated shape of the postgastrula embryo. This behavior has been termed convergence and extension [98]. Convergence and extension movements occur also during other stages of development and organogenesis to form elongated structures [40]. The non-canonical Wnt pathway has been found to be central to the regulation of this movement during gastrulation and several downstream effectors have been characterized, including the small GTPases Rho, Rac and Cdc42 [99–101]. In addition, two members of the Src-family of kinases, Fyn and Yes appear to converge on RhoA and knock down of these two proteins via an antisense approach leads to a phenotype similar to the phenotype after interference with the non-canonical Wnt pathway [102]. To further characterize the effect of the Fyn/Yes knock down on signaling during this essential morphogenetic movement, the group of den Hertog compared the phosphoproteome of Fyn/Yes knock down embryos to the phosphoproteome of wild type embryos [91]. Using an automated titanium dioxide-based LC-MS/MS set-up to enrich for phosphorylated peptides [90], they were able to identify 348 phosphoproteins. 69 of these proteins were found to be downregulated and 72 proteins upregulated in the Fyn/Yes deficient embryos. Several of the differentially regulated proteins found in this screen have already -directly or indirectly- been implicated in the regulation of gastrulation movements and/or in the reorganization of the cytoskeleton. In addition this study provides many new leads to further characterize the signaling network that regulates convergence and extension movements during development.
The last decades have provided a large pool of mutants and antisense tools to manipulate patterning and morphogenetic events in the embryo. Combined with the continuous improvements of proteomic techniques and the increasing availability of proteomic facilities this will certainly lead to an increase in comparative proteome studies of mutant or knock down embryos. In addition, comparative studies on isolated tissues of an embryo might also be possible. Most notably, amphibian embryos like Xenopus laevis are known for the ease with which relatively high amounts of different tissues can be manually isolated. Manual isolation has been employed in many different contexts, e.g. to construct tissue specific libraries, to compare expression of marker genes or for antibody-based comparison of protein levels [103–105] and should also be suitable for proteomic studies. Another technique that allows to collect different tissues from embryos is laser-assisted microdissection (LAM) [106]. This method allows to cut specific regions from tissue sections and can provide sufficient material for proteomic analysis [107, 108]. So far LAM has been mainly used in clinical applications. However it has already been applied to isolate tissue fragments from Xenopus laevis embryos for subsequent mRNA isolation, demonstrating its applicability during early stages of development [109]. Another exciting technical advancement for tissue specific protein identification is the development of imaging mass spectrometry (IMS). This technique allows the direct detection of proteins by mass spectroscopy on histological sections [110]. In principle this method already provides the means to compare the distribution of multiple proteins between different tissues without their preceding isolation. While currently still lacking the necessary resolution and sensitivity for most applications in embryology, it has transformed the mass spectrometer into a veritable protein microscope and with frequent technical improvements and increasing availability IMS might become a valuable tool to study protein distribution in the embryo [111].
The examples cited above illustrate how comparative studies can provide novel candidates for proteins that participate in the regulation and execution of morphogenetic movements. 2D-gel-based approaches were used most commonly for good reasons, but it might be beneficial to additionally use peptide-based approaches to detect changes in protein concentration that are underrepresented in 2D-gels [80–82]. This becomes especially useful since it appears that the correlation between mRNA and protein levels is weak [112, 113] and therefore peptide based approaches might reveal protein differences that are not detectable through genomic approaches. In this regard it would be interesting to determine the relative importance of transcriptional versus translational/posttranslational regulation on protein concentration and function in the embryo. Selective isolation of phosphoproteins in the context of morphogenetic movements highlights the possibility to characterize specific subsets of proteins and to link thereby signaling to the regulation of downstream effectors [91]. With increasingly detailed annotation of proteins and the continuous development of protein-protein interaction and signaling pathway databases [114, 115] it will hopefully soon be possible to reconstruct tissue and/or stage specific signaling networks from such data. Other subsets of relevant proteins that could possibly be isolated through subfractionation approaches are for example membrane-bound proteins [64, 116]. Cells are in constant communication with their environment and differential expression or activity of surface proteins is very likely involved in many processes of morphogenesis, including for example cell adhesion, directed cell and tissue movement or tissue separation [117–119]. Isolation of such proteins will provide new candidates to link external signals to internal changes in the mechanical properties of cells. Furthermore, improved affinity purification methods allow isolating protein complexes within signaling networks and, combined with subsequent mass spectroscopy, to identify novel complex associated proteins [120, 121]. Potentially, such methods can also be used to monitor changes in complex compositions in comparative studies of different stages/tissues or mutated versus wild type embryos and thereby allow further insight into the regulatory networks that controls cell behavior.
Conclusion
Within just a few years proteomic techniques have been used in a variety of model organisms of developmental biology and in applications ranging from the development of species specific protein databases down to the isolation and identification of single proteins of interest. These pioneering studies demonstrate the usefulness of proteomic approaches and with increasing availability of proteomic facilities and technical expertise, such approaches offer exciting possibilities in many areas of embryology. These new possibilities -we believe- will strongly influence the study of morphogenesis. So far our understanding of the driving forces behind morphogenetic movements is largely based on detailed descriptions of changes in cell shape and protrusive activity as well as explantation/ablation techniques to elucidate their relative contribution to the forces that form the embryo. However, cell biology has already made incredible progress in the characterization of the protein components that determine the mechanical attributes of a cell, its internal architecture and its external interactions. Drawing from the immense wealth of cell biological studies, morphogenetic studies have also been extended to the investigation of some of the molecular regulators of cell mechanics. Proteomics provide now the means to systematically study the regulatory events that link patterning signals to the structural changes that determine tissue specific cell behavior. In the short term this will provide new candidate regulators of morphogenesis. In the longer term, the continuing improvements in proteomic techniques and data analysis and presentation will provide a more comprehensive picture of time and tissue specific protein composition and posttranslational modifications. This will allow for a systematic analysis of the active signaling networks in a given tissue at a given time point and form the necessary basis for a multidisciplinary approach that includes e.g. biomechanics and in vivo imaging, to decipher how these signals are coordinated to produce the forces that shape a complete organism from an undifferentiated ball of cells.
References
Maienschein J: Arguments for Experimentation in Biology. PSA 1986 1987, 2: 180–195.
Driesch H: Entwicklungsmechanische Studien I. Der Werth der beiden ersten Furchungszellen in der Echinodermentwicklung. Experimentelle Erzeugung von Theil und Doppelbildung. Zeitschrift fuer wissenschaftliche Zoologie 1892, 53: 160–178.
Spemann H, Mangold H: Ueber die Induktion von Embryonalanlagen durch Implantation artfremder Organisatoren. ArchMikroskAnat 1924, 100: 599–638.
Wolpert L: Positional information and pattern formation. Curr Top Dev Biol 1971, 6: 183–224.
Turing AM: The Chemical Basis of Morphogenesis. Philosophical Transactions of the Royal Society of London 1952, B237: 37–72.
Driever W, Nusslein-Volhard C: A gradient of bicoid protein in Drosophila embryos. Cell 1988, 54: 83–93.
Driever W, Siegel V, Nusslein-Volhard C: Autonomous determination of anterior structures in the early Drosophila embryo by the bicoid morphogen. Development 1990, 109: 811–820.
Tam PP, Loebel DA: Gene function in mouse embryogenesis: get set for gastrulation. Nat Rev Genet 2007, 8: 368–381.
Heasman J: Patterning the early Xenopus embryo. Development 2006, 133: 1205–1217.
Rose LS, Kemphues KJ: Early patterning of the C. elegans embryo. Annu Rev Genet 1998, 32: 521–545.
Reversade B, De Robertis EM: Regulation of ADMP and BMP2/4/7 at opposite embryonic poles generates a self-regulating morphogenetic field. Cell 2005, 123: 1147–1160.
Fjose A, Ellingsen S, Wargelius A, Seo HC: RNA interference: mechanisms and applications. Biotechnol Annu Rev 2001, 7: 31–57.
Heasman J: Morpholino oligos: making sense of antisense? Dev Biol 2002, 243: 209–214.
Klein SL, Gerhard DS, Wagner L, Richardson P, Schriml LM, Sater AK, Warren WC, McPherson JD: Resources for genetic and genomic studies of Xenopus. Methods Mol Biol 2006, 322: 1–16.
Ashburner M, Bergman CM: Drosophila melanogaster : a case study of a model genomic sequence and its consequences. Genome Res 2005, 15: 1661–1667.
Hillier LW, Coulson A, Murray JI, Bao Z, Sulston JE, Waterston RH: Genomics in C. elegans : so many genes, such a little worm. Genome Res 2005, 15: 1651–1660.
Sodergren E, Weinstock GM, Davidson EH, Cameron RA, Gibbs RA, Angerer RC, Angerer LM, Arnone MI, Burgess DR, Burke RD, Coffman JA, Dean M, Elphick MR, Ettensohn CA, Foltz KR, Hamdoun A, Hynes RO, Klein WH, Marzluff W, McClay DR, Morris RL, Mushegian A, Rast JP, Smith LC, Thorndyke MC, Vacquier VD, Wessel GM, Wray G, Zhang L, Elsik CG, Ermolaeva O, Hlavina W, Hofmann G, Kitts P, Landrum MJ, Mackey AJ, Maglott D, Panopoulou G, Poustka AJ, Pruitt K, Sapojnikov V, Song X, Souvorov A, Solovyev V, Wei Z, Whittaker CA, Worley K, Durbin KJ, Shen Y, Fedrigo O, Garfield D, Haygood R, Primus A, Satija R, Severson T, Gonzalez-Garay ML, Jackson AR, Milosavljevic A, Tong M, Killian CE, Livingston BT, Wilt FH, Adams N, Belle R, Carbonneau S, Cheung R, Cormier P, Cosson B, Croce J, Fernandez-Guerra A, Geneviere AM, Goel M, Kelkar H, Morales J, Mulner-Lorillon O, Robertson AJ, Goldstone JV, Cole B, Epel D, Gold B, Hahn ME, Howard-Ashby M, Scally M, Stegeman JJ, Allgood EL, Cool J, Judkins KM, McCafferty SS, Musante AM, Obar RA, Rawson AP, Rossetti BJ, Gibbons IR, Hoffman MP, Leone A, Istrail S, Materna SC, Samanta MP, Stolc V, Tongprasit W, Tu Q, Bergeron KF, Brandhorst BP, Whittle J, Berney K, Bottjer DJ, Calestani C, Peterson K, Chow E, Yuan QA, Elhaik E, Graur D, Reese JT, Bosdet I, Heesun S, Marra MA, Schein J, Anderson MK, Brockton V, Buckley KM, Cohen AH, Fugmann SD, Hibino T, Loza-Coll M, Majeske AJ, Messier C, Nair SV, Pancer Z, Terwilliger DP, Agca C, Arboleda E, Chen N, Churcher AM, Hallbook F, Humphrey GW, Idris MM, Kiyama T, Liang S, Mellott D, Mu X, Murray G, Olinski RP, Raible F, Rowe M, Taylor JS, Tessmar-Raible K, Wang D, Wilson KH, Yaguchi S, Gaasterland T, Galindo BE, Gunaratne HJ, Juliano C, Kinukawa M, Moy GW, Neill AT, Nomura M, Raisch M, Reade A, Roux MM, Song JL, Su YH, Townley IK, Voronina E, Wong JL, Amore G, Branno M, Brown ER, Cavalieri V, Duboc V, Duloquin L, Flytzanis C, Gache C, Lapraz F, Lepage T, Locascio A, Martinez P, Matassi G, Matranga V, Range R, Rizzo F, Rottinger E, Beane W, Bradham C, Byrum C, Glenn T, Hussain S, Manning G, Miranda E, Thomason R, Walton K, Wikramanayke A, Wu SY, Xu R, Brown CT, Chen L, Gray RF, Lee PY, Nam J, Oliveri P, Smith J, Muzny D, Bell S, Chacko J, Cree A, Curry S, Davis C, Dinh H, Dugan-Rocha S, Fowler J, Gill R, Hamilton C, Hernandez J, Hines S, Hume J, Jackson L, Jolivet A, Kovar C, Lee S, Lewis L, Miner G, Morgan M, Nazareth LV, Okwuonu G, Parker D, Pu LL, Thorn R, Wright R: The genome of the sea urchin Strongylocentrotus purpuratus . Science 2006, 314: 941–952.
Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P, Antonarakis SE, Attwood J, Baertsch R, Bailey J, Barlow K, Beck S, Berry E, Birren B, Bloom T, Bork P, Botcherby M, Bray N, Brent MR, Brown DG, Brown SD, Bult C, Burton J, Butler J, Campbell RD, Carninci P, Cawley S, Chiaromonte F, Chinwalla AT, Church DM, Clamp M, Clee C, Collins FS, Cook LL, Copley RR, Coulson A, Couronne O, Cuff J, Curwen V, Cutts T, Daly M, David R, Davies J, Delehaunty KD, Deri J, Dermitzakis ET, Dewey C, Dickens NJ, Diekhans M, Dodge S, Dubchak I, Dunn DM, Eddy SR, Elnitski L, Emes RD, Eswara P, Eyras E, Felsenfeld A, Fewell GA, Flicek P, Foley K, Frankel WN, Fulton LA, Fulton RS, Furey TS, Gage D, Gibbs RA, Glusman G, Gnerre S, Goldman N, Goodstadt L, Grafham D, Graves TA, Green ED, Gregory S, Guigo R, Guyer M, Hardison RC, Haussler D, Hayashizaki Y, Hillier LW, Hinrichs A, Hlavina W, Holzer T, Hsu F, Hua A, Hubbard T, Hunt A, Jackson I, Jaffe DB, Johnson LS, Jones M, Jones TA, Joy A, Kamal M, Karlsson EK, Karolchik D, Kasprzyk A, Kawai J, Keibler E, Kells C, Kent WJ, Kirby A, Kolbe DL, Korf I, Kucherlapati RS, Kulbokas EJ, Kulp D, Landers T, Leger JP, Leonard S, Letunic I, Levine R, Li J, Li M, Lloyd C, Lucas S, Ma B, Maglott DR, Mardis ER, Matthews L, Mauceli E, Mayer JH, McCarthy M, McCombie WR, McLaren S, McLay K, McPherson JD, Meldrim J, Meredith B, Mesirov JP, Miller W, Miner TL, Mongin E, Montgomery KT, Morgan M, Mott R, Mullikin JC, Muzny DM, Nash WE, Nelson JO, Nhan MN, Nicol R, Ning Z, Nusbaum C, O'Connor MJ, Okazaki Y, Oliver K, Overton-Larty E, Pachter L, Parra G, Pepin KH, Peterson J, Pevzner P, Plumb R, Pohl CS, Poliakov A, Ponce TC, Ponting CP, Potter S, Quail M, Reymond A, Roe BA, Roskin KM, Rubin EM, Rust AG, Santos R, Sapojnikov V, Schultz B, Schultz J, Schwartz MS, Schwartz S, Scott C, Seaman S, Searle S, Sharpe T, Sheridan A, Shownkeen R, Sims S, Singer JB, Slater G, Smit A, Smith DR, Spencer B, Stabenau A, Stange-Thomann N, Sugnet C, Suyama M, Tesler G, Thompson J, Torrents D, Trevaskis E, Tromp J, Ucla C, Ureta-Vidal A, Vinson JP, Von Niederhausern AC, Wade CM, Wall M, Weber RJ, Weiss RB, Wendl MC, West AP, Wetterstrand K, Wheeler R, Whelan S, Wierzbowski J, Willey D, Williams S, Wilson RK, Winter E, Worley KC, Wyman D, Yang S, Yang SP, Zdobnov EM, Zody MC, Lander ES: Initial sequencing and comparative analysis of the mouse genome. Nature 2002, 420: 520–562.
Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S, Nikaido I, Osato N, Saito R, Suzuki H, Yamanaka I, Kiyosawa H, Yagi K, Tomaru Y, Hasegawa Y, Nogami A, Schonbach C, Gojobori T, Baldarelli R, Hill DP, Bult C, Hume DA, Quackenbush J, Schriml LM, Kanapin A, Matsuda H, Batalov S, Beisel KW, Blake JA, Bradt D, Brusic V, Chothia C, Corbani LE, Cousins S, Dalla E, Dragani TA, Fletcher CF, Forrest A, Frazer KS, Gaasterland T, Gariboldi M, Gissi C, Godzik A, Gough J, Grimmond S, Gustincich S, Hirokawa N, Jackson IJ, Jarvis ED, Kanai A, Kawaji H, Kawasawa Y, Kedzierski RM, King BL, Konagaya A, Kurochkin IV, Lee Y, Lenhard B, Lyons PA, Maglott DR, Maltais L, Marchionni L, McKenzie L, Miki H, Nagashima T, Numata K, Okido T, Pavan WJ, Pertea G, Pesole G, Petrovsky N, Pillai R, Pontius JU, Qi D, Ramachandran S, Ravasi T, Reed JC, Reed DJ, Reid J, Ring BZ, Ringwald M, Sandelin A, Schneider C, Semple CA, Setou M, Shimada K, Sultana R, Takenaka Y, Taylor MS, Teasdale RD, Tomita M, Verardo R, Wagner L, Wahlestedt C, Wang Y, Watanabe Y, Wells C, Wilming LG, Wynshaw-Boris A, Yanagisawa M, Yang I, Yang L, Yuan Z, Zavolan M, Zhu Y, Zimmer A, Carninci P, Hayatsu N, Hirozane-Kishikawa T, Konno H, Nakamura M, Sakazume N, Sato K, Shiraki T, Waki K, Kawai J, Aizawa K, Arakawa T, Fukuda S, Hara A, Hashizume W, Imotani K, Ishii Y, Itoh M, Kagawa I, Miyazaki A, Sakai K, Sasaki D, Shibata K, Shinagawa A, Yasunishi A, Yoshino M, Waterston R, Lander ES, Rogers J, Birney E, Hayashizaki Y: Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 2002, 420: 563–573.
Amaya E: Xenomics. Genome Res 2005, 15: 1683–1691.
Antoshechkin I, Sternberg PW: The versatile worm: genetic and genomic resources for Caenorhabditis elegans research. Nat Rev Genet 2007, 8: 518–532.
Sprague J, Bayraktaroglu L, Bradford Y, Conlin T, Dunn N, Fashena D, Frazer K, Haendel M, Howe DG, Knight J, Mani P, Moxon SA, Pich C, Ramachandran S, Schaper K, Segerdell E, Shao X, Singer A, Song P, Sprunger B, Van Slyke CE, Westerfield M: The Zebrafish Information Network: the zebrafish model organism database provides expanded support for genotypes and phenotypes. Nucleic Acids Res 2008, 36: D768–72.
Stathopoulos A, Levine M: Genomic regulatory networks and animal development. Dev Cell 2005, 9: 449–462.
Loose M, Patient R: A genetic regulatory network for Xenopus mesendoderm formation. Dev Biol 2004, 271: 467–478.
Tomlin CJ, Axelrod JD: Biology by numbers: mathematical modelling in developmental biology. Nat Rev Genet 2007, 8: 331–340.
Holtfreter J: Gewebeaffinitaet, ein Mittel der embryonalen Formbildung. Arch Exp Zellforsch 1939, 23: 169–209.
Townes PL, Holtfreter J: Directed movements and selective adhesion of embryonic. amphibian cells. J Exp Zool 1955, 128: 53–120.
Steinberg MS: Does differential adhesion govern self-assembly processes in histogenesis? Equilibrium configurations and the emergence of a hierarchy among populations of embryonic cells. J Exp Zool 1970, 173: 395–433.
Steinberg MS: Reconstruction of tissues by dissociated cells. Some morphogenetic tissue movements and the sorting out of embryonic cells may have a common explanation. Science 1963, 141: 401–408.
Wheelock MJ, Johnson KR: Cadherins as modulators of cellular phenotype. Annu Rev Cell Dev Biol 2003, 19: 207–235.
Heasman J, Ginsberg D, Geiger B, Goldstone K, Pratt T, Yoshida-Noro C, Wylie C: A functional test for maternally inherited cadherin in Xenopus shows its importance in cell adhesion at the blastula stage. Development 1994, 120: 49–57.
Kurth T, Fesenko IV, Schneider S, Munchberg FE, Joos TO, Spieker TP, Hausen P: Immunocytochemical studies of the interactions of cadherins and catenins in the early Xenopus embryo. Dev Dyn 1999, 215: 155–169.
Reintsch WE, Habring-Mueller A, Wang RW, Schohl A, Fagotto F: beta-Catenin controls cell sorting at the notochord-somite boundary independently of cadherin-mediated adhesion. J Cell Biol 2005, 170: 675–686.
Medina A, Swain RK, Kuerner KM, Steinbeisser H: Xenopus paraxial protocadherin has signaling functions and is involved in tissue separation. Embo J 2004, 23: 3249–3258.
Wacker S, Grimm K, Joos T, Winklbauer R: Development and control of tissue separation at gastrulation in Xenopus . Dev Biol 2000, 224: 428–439.
Chen X, Gumbiner BM: Paraxial protocadherin mediates cell sorting and tissue morphogenesis by regulating C-cadherin adhesion activity. J Cell Biol 2006, 174: 301–313.
Gerhart J, Keller R: Region-specific cell activities in amphibian gastrulation. Annu Rev Cell Biol 1986, 2: 201–229.
Rohde LA, Heisenberg CP: Zebrafish gastrulation: cell movements, signals, and mechanisms. Int Rev Cytol 2007, 261: 159–192.
Nance J, Lee JY, Goldstein B: Gastrulation in C. elegans . WormBook 2005, 1–13.
Keller R: Mechanisms of elongation in embryogenesis. Development 2006, 133: 2291–2302.
Lecuit T, Le Goff L: Orchestrating size and shape during morphogenesis. Nature 2007, 450: 189–192.
Wallingford JB, Fraser SE, Harland RM: Convergent extension: the molecular control of polarized cell movement during embryonic development. Dev Cell 2002, 2: 695–706.
Franke JD, Montague RA, Kiehart DP: Nonmuscle myosin II generates forces that transmit tension and drive contraction in multiple tissues during dorsal closure. Curr Biol 2005, 15: 2208–2221.
Marston DJ, Goldstein B: Actin-based forces driving embryonic morphogenesis in Caenorhabditis elegans . Curr Opin Genet Dev 2006, 16: 392–398.
Grevengoed EE, Loureiro JJ, Jesse TL, Peifer M: Abelson kinase regulates epithelial morphogenesis in Drosophila . J Cell Biol 2001, 155: 1185–1198.
Rodriguez OC, Schaefer AW, Mandato CA, Forscher P, Bement WM, Waterman-Storer CM: Conserved microtubule-actin interactions in cell movement and morphogenesis. Nat Cell Biol 2003, 5: 599–609.
Revenu C, Athman R, Robine S, Louvard D: The co-workers of actin filaments: from cell structures to signals. Nat Rev Mol Cell Biol 2004, 5: 635–646.
Chhabra ES, Higgs HN: The many faces of actin: matching assembly factors with cellular structures. Nat Cell Biol 2007, 9: 1110–1121.
Pollard TD, Borisy GG: Cellular motility driven by assembly and disassembly of actin filaments. Cell 2003, 112: 453–465.
Glotzer M: The molecular requirements for cytokinesis. Science 2005, 307: 1735–1739.
Lanzetti L: Actin in membrane trafficking. Curr Opin Cell Biol 2007, 19: 453–458.
Dawes-Hoang RE, Parmar KM, Christiansen AE, Phelps CB, Brand AH, Wieschaus EF: folded gastrulation, cell shape change and the control of myosin localization. Development 2005, 132: 4165–4178.
Wallingford JB, Rowning BA, Vogeli KM, Rothbacher U, Fraser SE, Harland RM: Dishevelled controls cell polarity during Xenopus gastrulation. Nature 2000, 405: 81–85.
Lee JY, Marston DJ, Walston T, Hardin J, Halberstadt A, Goldstein B: Wnt/Frizzled signaling controls C. elegans gastrulation by activating actomyosin contractility. Curr Biol 2006, 16: 1986–1997.
Gates J, Mahaffey JP, Rogers SL, Emerson M, Rogers EM, Sottile SL, Van Vactor D, Gertler FB, Peifer M: Enabled plays key roles in embryonic epithelial morphogenesis in Drosophila. Development 2007, 134: 2027–2039.
Kwan KM, Kirschner MW: A microtubule-binding Rho-GEF controls cell morphology during convergent extension of Xenopus laevis . Development 2005, 132: 4599–4610.
Au CE, Bell AW, Gilchrist A, Hiding J, Nilsson T, Bergeron JJ: Organellar proteomics to create the cell map. Curr Opin Cell Biol 2007, 19: 376–385.
Rout MP, Aitchison JD, Suprapto A, Hjertaas K, Zhao Y, Chait BT: The yeast nuclear pore complex: composition, architecture, and transport mechanism. J Cell Biol 2000, 148: 635–651.
Gilchrist A, Au CE, Hiding J, Bell AW, Fernandez-Rodriguez J, Lesimple S, Nagaya H, Roy L, Gosline SJ, Hallett M, Paiement J, Kearney RE, Nilsson T, Bergeron JJ: Quantitative proteomics analysis of the secretory pathway. Cell 2006, 127: 1265–1281.
Yates JR 3rd, Gilchrist A, Howell KE, Bergeron JJ: Proteomics of organelles and large cellular structures. Nat Rev Mol Cell Biol 2005, 6: 702–714.
Collins SR, Kemmeren P, Zhao XC, Greenblatt JF, Spencer F, Holstege FC, Weissman JS, Krogan NJ: Toward a comprehensive atlas of the physical interactome of Saccharomyces cerevisiae . Mol Cell Proteomics 2007, 6: 439–450.
Li S, Armstrong CM, Bertin N, Ge H, Milstein S, Boxem M, Vidalain PO, Han JD, Chesneau A, Hao T, Goldberg DS, Li N, Martinez M, Rual JF, Lamesch P, Xu L, Tewari M, Wong SL, Zhang LV, Berriz GF, Jacotot L, Vaglio P, Reboul J, Hirozane-Kishikawa T, Li Q, Gabel HW, Elewa A, Baumgartner B, Rose DJ, Yu H, Bosak S, Sequerra R, Fraser A, Mango SE, Saxton WM, Strome S, Van Den Heuvel S, Piano F, Vandenhaute J, Sardet C, Gerstein M, Doucette-Stamm L, Gunsalus KC, Harper JW, Cusick ME, Roth FP, Hill DE, Vidal M: A map of the interactome network of the metazoan C. elegans . Science 2004, 303: 540–543.
Giot L, Bader JS, Brouwer C, Chaudhuri A, Kuang B, Li Y, Hao YL, Ooi CE, Godwin B, Vitols E, Vijayadamodar G, Pochart P, Machineni H, Welsh M, Kong Y, Zerhusen B, Malcolm R, Varrone Z, Collis A, Minto M, Burgess S, McDaniel L, Stimpson E, Spriggs F, Williams J, Neurath K, Ioime N, Agee M, Voss E, Furtak K, Renzulli R, Aanensen N, Carrolla S, Bickelhaupt E, Lazovatsky Y, DaSilva A, Zhong J, Stanyon CA, Finley RL Jr., White KP, Braverman M, Jarvie T, Gold S, Leach M, Knight J, Shimkets RA, McKenna MP, Chant J, Rothberg JM: A protein interaction map of Drosophila melanogaster . Science 2003, 302: 1727–1736.
Shin BK, Wang H, Yim AM, Le Naour F, Brichory F, Jang JH, Zhao R, Puravs E, Tra J, Michael CW, Misek DE, Hanash SM: Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function. J Biol Chem 2003, 278: 7607–7616.
Oh P, Li Y, Yu J, Durr E, Krasinska KM, Carver LA, Testa JE, Schnitzer JE: Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy. Nature 2004, 429: 629–635.
Blondeau F, Ritter B, Allaire PD, Wasiak S, Girard M, Hussain NK, Angers A, Legendre-Guillemin V, Roy L, Boismenu D, Kearney RE, Bell AW, Bergeron JJ, McPherson PS: Tandem MS analysis of brain clathrin-coated vesicles reveals their critical involvement in synaptic vesicle recycling. Proc Natl Acad Sci U S A 2004, 101: 3833–3838.
Collins MO, Husi H, Yu L, Brandon JM, Anderson CN, Blackstock WP, Choudhary JS, Grant SG: Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome. J Neurochem 2006, 97 Suppl 1: 16–23.
Wang Q, Woltjer RL, Cimino PJ, Pan C, Montine KS, Zhang J, Montine TJ: Proteomic analysis of neurofibrillary tangles in Alzheimer disease identifies GAPDH as a detergent-insoluble paired helical filament tau binding protein. Faseb J 2005, 19: 869–871.
Tay TL, Lin Q, Seow TK, Tan KH, Hew CL, Gong Z: Proteomic analysis of protein profiles during early development of the zebrafish, Danio rerio . Proteomics 2006, 6: 3176–3188.
Lucitt MB, Price TS, Pizarro A, Wu W, Yocum AK, Seiler C, Pack MA, Blair IA, Fitzgerald GA, Grosser T: Analysis of the zebrafish proteome during embryonic development. Mol Cell Proteomics 2008, 7: 981–994.
Seefeldt I, Nebrich G, Romer I, Mao L, Klose J: Evaluation of 2-DE protein patterns from pre- and postnatal stages of the mouse brain. Proteomics 2006, 6: 4932–4939.
Mizukami M, Kanamoto T, Souchelnytskyi N, Kiuchi Y: Proteome profiling of embryo chick retina. Proteome Sci 2008, 6: 3.
Greene ND, Leung KY, Wait R, Begum S, Dunn MJ, Copp AJ: Differential protein expression at the stage of neural tube closure in the mouse embryo. J Biol Chem 2002, 277: 41645–41651.
Taraszka JA, Kurulugama R, Sowell RA, Valentine SJ, Koeniger SL, Arnold RJ, Miller DF, Kaufman TC, Clemmer DE: Mapping the proteome of Drosophila melanogaster : analysis of embryos and adult heads by LC-IMS-MS methods. J Proteome Res 2005, 4: 1223–1237.
Link V, Carvalho L, Castanon I, Stockinger P, Shevchenko A, Heisenberg CP: Identification of regulators of germ layer morphogenesis using proteomics in zebrafish. J Cell Sci 2006, 119: 2073–2083.
Gong L, Puri M, Unlu M, Young M, Robertson K, Viswanathan S, Krishnaswamy A, Dowd SR, Minden JS: Drosophila ventral furrow morphogenesis: a proteomic analysis. Development 2004, 131: 643–656.
Usami M, Mitsunaga K, Nakazawa K: Comparative proteome analysis of the embryo proper and yolk sac membrane of day 11.5 cultured rat embryos. Birth Defects Res B Dev Reprod Toxicol 2007, 80: 383–395.
Roux MM, Radeke MJ, Goel M, Mushegian A, Foltz KR: 2DE identification of proteins exhibiting turnover and phosphorylation dynamics during sea urchin egg activation. Dev Biol 2008, 313: 630–647.
Domanski D, Helbing CC: Analysis of the Rana catesbeiana tadpole tail fin proteome and phosphoproteome during T3-induced apoptosis: identification of a novel type I keratin. BMC Dev Biol 2007, 7: 94.
Gygi SP, Corthals GL, Zhang Y, Rochon Y, Aebersold R: Evaluation of two-dimensional gel electrophoresis-based proteome analysis technology. Proc Natl Acad Sci U S A 2000, 97: 9390–9395.
Wilkins MR, Gasteiger E, Sanchez JC, Bairoch A, Hochstrasser DF: Two-dimensional gel electrophoresis for proteome projects: the effects of protein hydrophobicity and copy number. Electrophoresis 1998, 19: 1501–1505.
Santoni V, Molloy M, Rabilloud T: Membrane proteins and proteomics: un amour impossible? Electrophoresis 2000, 21: 1054–1070.
Link AJ, Eng J, Schieltz DM, Carmack E, Mize GJ, Morris DR, Garvik BM, Yates JR 3rd: Direct analysis of protein complexes using mass spectrometry. Nat Biotechnol 1999, 17: 676–682.
Gevaert K, Van Damme P, Ghesquiere B, Impens F, Martens L, Helsens K, Vandekerckhove J: A la carte proteomics with an emphasis on gel-free techniques. Proteomics 2007, 7: 2698–2718.
Martens L, Van Damme P, Van Damme J, Staes A, Timmerman E, Ghesquiere B, Thomas GR, Vandekerckhove J, Gevaert K: The human platelet proteome mapped by peptide-centric proteomics: a functional protein profile. Proteomics 2005, 5: 3193–3204.
Liu H, Lin D, Yates JR 3rd: Multidimensional separations for protein/peptide analysis in the post-genomic era. Biotechniques 2002, 32: 898, 900, 902 passim.
Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining Protein-Based IMAC, Peptide-Based IMAC, and MudPIT for Efficient Phosphoproteomic Analysis. J Proteome Res 2008, 7: 1346–1351.
Puente LG, Voisin S, Lee RE, Megeney LA: Reconstructing the regulatory kinase pathways of myogenesis from phosphopeptide data. Mol Cell Proteomics 2006, 5: 2244–2251.
Zhai B, Villen J, Beausoleil SA, Mintseris J, Gygi SP: Phosphoproteome analysis of Drosophila melanogaster embryos. J Proteome Res 2008, 7: 1675–1682.
Lemeer S, Pinkse MW, Mohammed S, van Breukelen B, den Hertog J, Slijper M, Heck AJ: Online automated in vivo zebrafish phosphoproteomics: from large-scale analysis down to a single embryo. J Proteome Res 2008, 7: 1555–1564.
Lemeer S, Jopling C, Gouw JW, Mohammed S, Heck AJ, Slijper M, den Hertog J: Comparative phosphoproteomics of zebrafish Fyn/Yes morpholino knockdown embryos. Mol Cell Proteomics 2008.
Ballif BA, Villen J, Beausoleil SA, Schwartz D, Gygi SP: Phosphoproteomic analysis of the developing mouse brain. Mol Cell Proteomics 2004, 3: 1093–1101.
Balcerzak M, Malinowska A, Thouverey C, Sekrecka A, Dadlez M, Buchet R, Pikula S: Proteome analysis of matrix vesicles isolated from femurs of chicken embryo. Proteomics 2008, 8: 192–205.
Olson SK, Bishop JR, Yates JR, Oegema K, Esko JD: Identification of novel chondroitin proteoglycans in Caenorhabditis elegans: embryonic cell division depends on CPG-1 and CPG-2. J Cell Biol 2006, 173: 985–994.
Gritsman K, Zhang J, Cheng S, Heckscher E, Talbot WS, Schier AF: The EGF-CFC protein one-eyed pinhead is essential for nodal signaling. Cell 1999, 97: 121–132.
Feldman B, Dougan ST, Schier AF, Talbot WS: Nodal-related signals establish mesendodermal fate and trunk neural identity in zebrafish. Curr Biol 2000, 10: 531–534.
Matsui T, Maeda M, Doi Y, Yonemura S, Amano M, Kaibuchi K, Tsukita S: Rho-kinase phosphorylates COOH-terminal threonines of ezrin/radixin/moesin (ERM) proteins and regulates their head-to-tail association. J Cell Biol 1998, 140: 647–657.
Keller RE, Danilchik M, Gimlich R, Shih J: The function and mechanism of convergent extension during gastrulation of Xenopus laevis . J Embryol Exp Morphol 1985, 89 Suppl: 185–209.
Habas R, Kato Y, He X: Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. Cell 2001, 107: 843–854.
Habas R, Dawid IB, He X: Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation. Genes Dev 2003, 17: 295–309.
Choi SC, Han JK: Xenopus Cdc42 regulates convergent extension movements during gastrulation through Wnt/Ca2+ signaling pathway. Dev Biol 2002, 244: 342–357.
Jopling C, den Hertog J: Fyn/Yes and non-canonical Wnt signalling converge on RhoA in vertebrate gastrulation cell movements. EMBO Rep 2005, 6: 426–431.
Blumberg B, Wright CV, De Robertis EM, Cho KW: Organizer-specific homeobox genes in Xenopus laevis embryos. Science 1991, 253: 194–196.
Brieher WM, Gumbiner BM: Regulation of C-cadherin function during activin induced morphogenesis of Xenopus animal caps. J Cell Biol 1994, 126: 519–527.
Suri C, Haremaki T, Weinstein DC: Inhibition of mesodermal fate by Xenopus HNF3beta/FoxA2. Dev Biol 2004, 265: 90–104.
Chimge NO, Ruddle F, Bayarsaihan D: Laser-assisted microdissection (LAM) in developmental biology. J Exp Zoolog B Mol Dev Evol 2007, 308: 113–118.
Li C, Hong Y, Tan YX, Zhou H, Ai JH, Li SJ, Zhang L, Xia QC, Wu JR, Wang HY, Zeng R: Accurate qualitative and quantitative proteomic analysis of clinical hepatocellular carcinoma using laser capture microdissection coupled with isotope-coded affinity tag and two-dimensional liquid chromatography mass spectrometry. Mol Cell Proteomics 2004, 3: 399–409.
Umar A, Luider TM, Foekens JA, Pasa-Tolic L: NanoLC-FT-ICR MS improves proteome coverage attainable for approximately 3000 laser-microdissected breast carcinoma cells. Proteomics 2007, 7: 323–329.
Imamichi Y, Lahr G, Wedlich D: Laser-mediated microdissection of paraffin sections from Xenopus embryos allows detection of tissue-specific expressed mRNAs. Dev Genes Evol 2001, 211: 361–366.
Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM: Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat Med 2001, 7: 493–496.
Cornett DS, Reyzer ML, Chaurand P, Caprioli RM: MALDI imaging mass spectrometry: molecular snapshots of biochemical systems. Nat Methods 2007, 4: 828–833.
Gygi SP, Rochon Y, Franza BR, Aebersold R: Correlation between protein and mRNA abundance in yeast. Mol Cell Biol 1999, 19: 1720–1730.
Anderson L, Seilhamer J: A comparison of selected mRNA and protein abundances in human liver. Electrophoresis 1997, 18: 533–537.
Bork P, Jensen LJ, von Mering C, Ramani AK, Lee I, Marcotte EM: Protein interaction networks from yeast to human. Curr Opin Struct Biol 2004, 14: 292–299.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo , and site-specific phosphorylation dynamics in signaling networks. Cell 2006, 127: 635–648.
Zhang W, Zhou G, Zhao Y, White MA: Affinity enrichment of plasma membrane for proteomics analysis. Electrophoresis 2003, 24: 2855–2863.
Tepass U, Godt D, Winklbauer R: Cell sorting in animal development: signalling and adhesive mechanisms in the formation of tissue boundaries. Curr Opin Genet Dev 2002, 12: 572–582.
Nagel M, Tahinci E, Symes K, Winklbauer R: Guidance of mesoderm cell migration in the Xenopus gastrula requires PDGF signaling. Development 2004, 131: 2727–2736.
Shook D, Keller R: Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mech Dev 2003, 120: 1351–1383.
Gingras AC, Gstaiger M, Raught B, Aebersold R: Analysis of protein complexes using mass spectrometry. Nat Rev Mol Cell Biol 2007, 8: 645–654.
Rigaut G, Shevchenko A, Rutz B, Wilm M, Mann M, Seraphin B: A generic protein purification method for protein complex characterization and proteome exploration. Nat Biotechnol 1999, 17: 1030–1032.
Goishi K, Shimizu A, Najarro G, Watanabe S, Rogers R, Zon LI, Klagsbrun M: AlphaA-crystallin expression prevents gamma-crystallin insolubility and cataract formation in the zebrafish cloche mutant lens. Development 2006, 133: 2585–2593.
Tabuse Y, Nabetani T, Tsugita A: Proteomic analysis of protein expression profiles during Caenorhabditis elegans development using two-dimensional difference gel electrophoresis. Proteomics 2005, 5: 2876–2891.
Agudo D, Gomez-Esquer F, Diaz-Gil G, Martinez-Arribas F, Delcan J, Schneider J, Palomar MA, Linares R: Proteomic analysis of the Gallus gallus embryo at stage-29 of development. Proteomics 2005, 5: 4946–4957.
Hartl D, Irmler M, Romer I, Mader MT, Mao L, Zabel C, de Angelis MH, Beckers J, Klose J: Transcriptome and proteome analysis of early embryonic mouse brain development. Proteomics 2008, 8: 1257–1265.
Zhou Q, Wu C, Dong B, Liu F, Xiang J: The Encysted Dormant Embryo Proteome of Artemia sinica. Mar Biotechnol (NY) 2008, 10: 438–446.
Wang W, Meng B, Chen W, Ge X, Liu S, Yu J: A proteomic study on postdiapaused embryonic development of brine shrimp ( Artemia franciscana ). Proteomics 2007, 7: 3580–3591.
Acknowledgements
CAM is Canada Research Chair. This work was supported by an operating grant from the Canadian Institute of Health Research (MOP-68970 to CAM).
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WER and CAM co-wrote the manuscript and approved the final version.
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Reintsch, W.E., Mandato, C.A. Deciphering animal development through proteomics: requirements and prospects. Proteome Sci 6, 21 (2008). https://doi.org/10.1186/1477-5956-6-21
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DOI: https://doi.org/10.1186/1477-5956-6-21