Abstract
Genomics tools are revolutionizing the way we study developmental processes. Microarrays and RNA-Seq allow the sensitive, quantitative and global analysis of gene expression patterns. Instead of examining a few select genes, it is now routine to generate global gene expression profiles of developing systems. The early experiments examined entire developing organs, thereby identifying, for example, all transcription factors, growth factors, and receptors expressed. Subsequent experiments dramatically improved the genomics analysis by providing higher spatio-temporal resolution. Organ development is remarkably complex, with discrete substructures, a developmental time course of events, and the simultaneous differentiation of discrete cell types. It is not possible, therefore, to homogenize the developing organ, apply genomics tools, and derive deep insight. Laser capture microdissection allows the purification of single developmental compartments. Transgenic mice with gene specific promoters driving the expression of markers, such as green fluorescent protein, can be used to purify specific cell types from developing organs. Even higher resolution analysis can be carried out with tools that allow the gene expression profiling of single cells. The use of these genomics approaches produces enormous volumes of data that need to be captured, annotated in a systematic way, stored, integrated and analyzed, using the resources of biomedical informatics.
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Bafico A, et al. Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/arrow. Nat Cell Biol. 2001;3(7):683–6.
Brady G, Iscove NN. Construction of cDNA libraries from single cells. Methods Enzymol. 1993;225:611–23.
Brunskill EW, Potter SS. Gene expression programs of mouse endothelial cells in kidney development and disease. PLoS One. 2010;5(8):e12034.
Brunskill EW, Potter SS. RNA-Seq defines novel genes, RNA processing patterns and enhancer maps for the early stages of nephrogenesis: Hox supergenes. Dev Biol. 2012;368:4–17.
Brunskill EW, et al. Atlas of gene expression in the developing kidney at microanatomic resolution. Dev Cell. 2008;15(5):781–91.
Brunskill EW, et al. Defining the molecular character of the developing and adult kidney podocyte. PLoS One. 2011a;6(9):e24640.
Brunskill EW, et al. Genes that confer the identity of the renin cell. J Am Soc Nephrol. 2011b;22(12):2213–25.
Carroll TJ, et al. Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system. Dev Cell. 2005;9(2):283–92.
Chai Y, Maxson Jr RE. Recent advances in craniofacial morphogenesis. Dev Dyn. 2006;235(9):2353–75.
Challen G, et al. Temporal and spatial transcriptional programs in murine kidney development. Physiol Genomics. 2005;23(2):159–71.
Chang HH, et al. Transcriptome-wide noise controls lineage choice in mammalian progenitor cells. Nature. 2008;453(7194):544–7.
Cherry TJ, et al. Development and diversification of retinal amacrine interneurons at single cell resolution. Proc Natl Acad Sci U S A. 2009;106(23):9495–500.
Chubb JR, et al. Transcriptional pulsing of a developmental gene. Curr Biol. 2006;16(10):1018–25.
Cloonan N, et al. Stem cell transcriptome profiling via massive-scale mRNA sequencing. Nat Methods. 2008;5(7):613–19.
Copois V, et al. Assessment of RNA quality extracted from laser-captured tissues using miniaturized capillary electrophoresis. Lab Invest. 2003;83(4):599–602.
Costantini F, Kopan R. Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Dev Cell. 2010;18(5):698–712.
De Santa F, et al. A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biol. 2010;8(5):e184.
Elowitz MB, et al. Stochastic gene expression in a single cell. Science. 2002;297(5584):1183–6.
Feng W, et al. Spatial and temporal analysis of gene expression during growth and fusion of the mouse facial prominences. PLoS One. 2009;4(12):e8066.
Golding I, et al. Real-time kinetics of gene activity in individual bacteria. Cell. 2005;123(6):1025–36.
Iscove NN, et al. Representation is faithfully preserved in global cDNA amplified exponentially from sub-picogram quantities of mRNA. Nat Biotechnol. 2002;20(9):940–3.
Jackson DA, et al. Visualization of focal sites of transcription within human nuclei. EMBO J. 1993;12(3):1059–65.
Kamme F, et al. Single-cell microarray analysis in hippocampus CA1: demonstration and validation of cellular heterogeneity. J Neurosci. 2003;23(9):3607–15.
Kane MD, et al. Assessment of the sensitivity and specificity of oligonucleotide (50mer) microarrays. Nucleic Acids Res. 2000;28(22):4552–7.
Keller G, et al. Nephron number in patients with primary hypertension. N Engl J Med. 2003;348(2):101–8.
Kim TK, et al. Widespread transcription at neuronal activity-regulated enhancers. Nature. 2010;465(7295):182–7.
Ko MS, Nakauchi H, Takahashi N. The dose dependence of glucocorticoid-inducible gene expression results from changes in the number of transcriptionally active templates. EMBO J. 1990;9(9):2835–42.
Kobayashi A, et al. Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney development. Development. 2005;132(12):2809–23.
Kurn N, et al. Novel isothermal, linear nucleic acid amplification systems for highly multiplexed applications. Clin Chem. 2005;51(10):1973–81.
Mao B, et al. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001;411(6835):321–5.
McGinnis N, Kuziora MA, McGinnis W. Human Hox-4.2 and Drosophila deformed encode similar regulatory specificities in Drosophila embryos and larvae. Cell. 1990;63(5):969–76.
Mortazavi A, et al. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods. 2008;5(7):621–8.
Nagalakshmi U, et al. The transcriptional landscape of the yeast genome defined by RNA sequencing. Science. 2008;320(5881):1344–9.
Novick A, Weiner M. Enzyme induction as an all-or-none phenomenon. Proc Natl Acad Sci U S A. 1957;43(7):553–66.
Osborne CS, et al. Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet. 2004;36(10):1065–71.
Ozbudak EM, et al. Regulation of noise in the expression of a single gene. Nat Genet. 2002;31(1):69–73.
Poladia DP, et al. Link between reduced nephron number and hypertension: studies in a mutant mouse model. Pediatr Res. 2006;59(4 Pt 1):489–93.
Potter SS, et al. Laser capture-microarray analysis of Lim1 mutant kidney development. Genesis. 2007;45(7):432–9.
Raj A, et al. Imaging individual mRNA molecules using multiple singly labeled probes. Nat Methods. 2008;5(10):877–9.
Ross IL, Browne CM, Hume DA. Transcription of individual genes in eukaryotic cells occurs randomly and infrequently. Immunol Cell Biol. 1994;72(2):177–85.
Schmidt-Ott KM, et al. Novel regulators of kidney development from the tips of the ureteric bud. J Am Soc Nephrol. 2005;16(7):1993–2002.
Schwab K, et al. A catalogue of gene expression in the developing kidney. Kidney Int. 2003;64(5):1588–604.
Schwab K, et al. Comprehensive microarray analysis of Hoxa11/Hoxd11 mutant kidney development. Dev Biol. 2006;293(2):540–54.
Self M, et al. Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. EMBO J. 2006;25(21):5214–28.
Shawlot W, Behringer RR. Requirement for Lim1 in head-organizer function. Nature. 1995;374(6521):425–30.
Stark K, et al. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature. 1994;372(6507):679–83.
Stuart RO, Bush KT, Nigam SK. Changes in global gene expression patterns during development and maturation of the rat kidney. Proc Natl Acad Sci U S A. 2001;98(10):5649–54.
Stuart RO, Bush KT, Nigam SK. Changes in gene expression patterns in the ureteric bud and metanephric mesenchyme in models of kidney development. Kidney Int. 2003;64(6):1997–2008.
Takasuka N, et al. Dynamic changes in prolactin promoter activation in individual living lactotrophic cells. Endocrinology. 1998;139(3):1361–8.
Tsuboi A, et al. Olfactory neurons expressing closely linked and homologous odorant receptor genes tend to project their axons to neighboring glomeruli on the olfactory bulb. J Neurosci. 1999;19(19):8409–18.
Vassar R, Ngai J, Axel R. Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium. Cell. 1993;74(2):309–18.
Wansink DG, et al. Fluorescent labeling of nascent RNA reveals transcription by RNA polymerase II in domains scattered throughout the nucleus. J Cell Biol. 1993;122(2):283–93.
Wernet MF, et al. Stochastic spineless expression creates the retinal mosaic for colour vision. Nature. 2006;440(7081):174–80.
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This work was supported in part by NIH grant number RC4-DK090891.
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Brunskill, E.W., Potter, A.S., Potter, S.S. (2012). Defining Genetic Blueprints – Kidney and Craniofacial Development. In: Hutton, J. (eds) Pediatric Biomedical Informatics. Translational Bioinformatics, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5149-1_18
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DOI: https://doi.org/10.1007/978-94-007-5149-1_18
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