Abstract
The repeated appearance of somites is one of the most fascinating aspects of vertebrate embryogenesis. Recent studies identified complex regulatory circuits that provide the molecular basis for the “clock and wave front” model, postulated almost 30 years ago by Cooke and Zeeman. The highly coordinated process of somite formation involves several networks of molecular cascades including the Delta/Notch, Wnt, FGF and retinoid signalling pathways. Studies in mouse, Xenopus and especially chicken over the last decade have helped to understand the role and interactions of these pathways in somitogenesis. More recently, this has been supplemented by experiments in zebrafish. This animal model offers the possibility of performing large scale mutagenesis screens to identify novel factors and pathways involved in somitogenesis. Molecular cloning of zebrafish somite mutants mainly resulted in genes that belong to the Delta/Notch pathway and therefore underlined the importance of this pathway during somitogenesis. The fact that other pathways have not yet been identified by genetic screening in this species was assumed to be caused by functional redundancy of duplicated genes in zebrafish. In 2000, a large-scale mutagenesis screen has been initiated in Kyoto, Japan using the related teleost medaka (Oryzias latipes). In this screen, mutants with unique phenotypes have been identified, which have not been described in zebrafish or mouse. In this chapter, we will review the progress that has been made in understanding the molecular control of somite formation in zebrafish and will discuss recent efforts to screen for novel phenotypes using medaka somitogenesis mutants.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Driever W, Solnica-Krezel L, Schier AF et al. A genetic screen for mutations affecting embryogenesis in zebrafish. Development 1996; 123:37–46.
Haffter P, Granato M, Brand M et al. The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development 1996; 123:1–36.
Knaut H, Werz C, Geisler R et al. Tübingen 2000 Screen Consortium. A zebrafish homologue of the chemokine receptor Cxcr4 is a germ-cell guidance receptor. Nature 2003; 421:279–82.
Pourquie O, Tam PP. A nomenclature for prospective somites and phases of cyclic gene expression in the presomitic mesoderm. Dev Cell 2001; 1:619–20.
Karlstrom RO, Talbot WS, Schier AF. Comparative synteny cloning of zebrafish you-too: mutations in the Hedgehog target gli2 affect ventral forebrain patterning. Genes Dev 1999; 13:388–93.
Schauerte HE, van Eeden FJM, Fricke C et al. Sonic hedgehog is not required for the induction of medial floor plate cells in the zebrafish. Development 1998; 125:2983–93.
Nakano Y, Kim HR, Kawakami A et al. Inactivation of dispatched 1 by the chameleon mutation disrupts Hedgehog signalling in the zebrafish embryo. Dev Biol 2004; 269:381–92.
Baxendale S, Davison C, Muxworthy C et al. The B-cell maturation factor Blimp-1 specifies vertebrate slow-twitch muscle fiber identity in response to Hedgehog signaling. Nat Genet 2004; 36:88–93.
Stickney HL, Barresi MJ, Devoto SH. Somite development in zebrafish. Dev Dyn 2000; 219:287–303.
Nikaido M, Kawakami A, Sawada A et al. Tbx24, encoding a T-box protein, is mutated in the zebrafish somite-segmentation mutant fused somites. Nat Genet 2002; 31:195–9.
Holley SA, Geisler R, Nüsslein-Volhard C. Control of her1 expression during zebrafish somitogenesis by a Delta-dependent oscillator and an independent wave-front activity. Genes Dev 2000; 14:1678–90.
Holley SA, Julich D, Rauch GJ et al. Her1 and the notch pathway function within the oscillator mechanism that regulated zebrafish somitogenesis. Development 2002; 129:1175–83.
Julich D, Hwee Lim C, Round J et al. Tubingen 2000 Screen Consortium. beamter/deltaC and the role of Notch ligands in the zebrafish somite segmentation, hindbrain neurogenesis and hypochord differentiation. Dev Biol 2005; 286:391–404.
Itoh M, Kim CH, Palardy G et al. Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. Dev Cell 2003; 4:67–82.
Griffin KJ, Amacher SL, Kimmel CB et al. Molecular identification of spadetail: regulation of zebrafish trunk and tail mesoderm formation by T-box genes. Development 1998; 125:3379–88.
Julich D, Geisler R, Holley SA. Tubingen 2000 Screen Consortium. Integrinalpha5 and delta/notch signaling have complementary spatiotemporal requirements during zebrafish somitogenesis. Dev Cell 2005; 8:575–86.
Koshida S, Kishimoto Y, Ustumi H et al. Integrinalpha5-dependent fibronectin accumulation for maintenance of somite boundaries in zebrafish embryos. Dev Cell 2005; 8:587–98.
Cooke J, Zeeman EC. A clock and wavefront model for control of the number of repeated structures during animal morphogenesis. J Theor Biol 1976; 58:455–76.
Jiang YJ, Brand M, Heisenberg CP et al. Mutations affecting neurogenesis and brain morphology in the zebrafish, Danio rerio. Development 1996; 123:205–16.
Oates AC, Ho RK. Hairy/E(spl)-related (Her) genes are central components of the segmentation oscillator and display redundancy with the Delta/notch signaling pathway in the formation of anterior segmental boundaries in the zebrafish. Development 2002; 129:2929–46.
Gajewski M, Sieger D, Alt B et al. Anterior and posterior waves of cyclic her1 gene expression are differentially regulated in the presomitic mesoderm of zebrafish. Development 2003; 130:4269–78.
Winkler C, Elmasri H, Klamt B et al. Characterization of hey bHLH genes in teleost fish. Dev Genes Evol 2003; 213:541–53.
Holley SA, Takeda H. Catching a wave: the oscillator and wavefront that create the zebrafish somite. Semin Cell Dev Biol 2002; 13:481–88.
Henry CA, Urban MK, Dill KK et al. Two linked hairy/Enhancer of split-related zebrafish genes, her1 and her7, function together to refine alternating somite boundaries. Development 2002; 129:3693–704.
Sieger D, Tautz D, Gajewski M. The role of Suppressor of Hairless in Notch mediated signaling during zebrafish somitogenesis. Mech Dev 2003; 120:1083–94.
Sieger D, Tautz D, Gajewski M. her11 is involved in the somitogenesis clock in zebrafish. Dev Genes Evol 2004; 214:393–406.
Takke C, Campos-Ortega JA. her1, a zebrafish pair-rule like gene, acts downstream of notch signalling to control somite development. Development 1999; 126:3005–14.
Horikawa K, Ishimatsu K, Yoshimoto E et al. Noise-resistant and synchronized oscillation of the segmentation clock. Nature 2006; 441:719–23.
Jiang YJ, Aerne BL, Smithers L et al. Notch signaling and the synchronization of the somite segmentation clock. Nature 2000; 408:475–9.
Lewis J. Autoinhibition with transcriptional delay: a simple mechanism for the zebrafish somitogenesis oscillator. Curr Biol 2003; 13:1398–408.
Sawada A, Fritz A, Jiang YJ et al. Zebrafish Mesp family genes, mesp-a and mesp-b are segmentally expressed in the presomitic mesoderm and Mesp-b confers the anterior identity to the developing somites. Development 2000; 127:1691–702.
Dubrulle J, McGrew MJ, Pourquie O. FGF signaling controls somite boundary position and regulates segmentation clock control of spatiotemporal Hox gene activation. Cell 2001; 106:219–32.
Sawada A, Shinya M, Jiang YJ et al. Fgf/MAPK signaling is a crucial positional cue in somite boundary formation. Development 2001; 128:4873–80.
Reifers F, Bohli H, Walsh EC et al. Fgf8 is mutated in zebrafish acerebellar (ace) mutants and is required for maintenance of midbrain-hindbrain boundary development and somitogenesis. Development 1998; 125:2381–95.
Draper BW, Stock DW, Kimmel CB. Zebrafish fgf24 functions with fgf8 to promote posterior mesodermal development. Development 2003; 130:4639–54.
Kawamura A, Koshida S, Hijikata H et al. Zebrafish hairy/enhancer of split protein links FGF signaling to cyclic gene expression in the periodic segmentation of somites. Genes Dev 2005; 19:1156–61.
Sieger D, Ackermann B, Winkler C et al. her1 and her13.2 are jointly required for somitic border specification along the entire axis of the fish embryo. Dev Biol 2006; 293:242–51.
Kawamura A, Koshida S, Hijikata H et al. Groucho-associated transcriptional repressor ripply1 is required for proper transition from the presomitic mesoderm to somites. Dev Cell 2005; 9:735–44.
Aulehla A, Wehrle C, Brand-Saberi B et al. Wnt3a plays a major role in the segmentation clock controlling somitogenesis. Dev Cell 2003; 4:395–406.
Galceran J, Sustmann C, Hsu SC et al. LEF1-mediated regulation of Delta-like1 links Wnt and Notch signaling in somitogenesis. Genes Dev 2004; 18:2718–23.
Hofmann M, Schuster-Gossler K, Watabe-Rudolph M et al. WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dll1 expression in the presomitic mesoderm of mouse embryos. Genes Dev 2004; 18:2712–17.
Aulehla A, Herrmann BG. Segmentation in vertebrates: clock and gradient finally joined. Genes Dev 2004; 18:2060–67.
Rauch GJ, Hammerschmidt M, Blader P et al. Wnt5 is required for tail formation in the zebrafish embryo. Cold Spring Harb Symp Quant Biol 1997; 62:227–34.
Heisenberg CP, Houart C, Take-Uchi M et al. A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon. Genes Dev 2001; 15:1427–34.
Krauss S, Korzh V, Fjose A et al. Expression of four zebrafish wnt-related genes during embryogenesis. Development 1992; 116:249–59.
Buckles GR, Thorpe CJ, Ramel MC et al. Combinatorial Wnt control of zebrafish midbrain-hindbrain boundary formation. Mech Dev 2004; 121:437–47.
Brent AE. Somite formation: Where Left meets right. Current Biology 2005; 15:468–70.
Kawakami Y, Raya A, Raya RM et al. Retinoic acid signalling links left-right asymmetric patterning and bilaterally symmetric somitogenesis in the zebrafish embryo. Nature 2005; 435:165–71.
Thermes V, Grabher C, Ristoratore F et al. I-SceI meganuclease mediates highly efficient transgenesis in fish. Mech Dev 2002; 118:91–8.
Grabher C, Henrich T, Sasado T et al. Transposon-mediated enhancer trapping in medaka. Gene 2003; 322:57–66.
Hong Y, Winkler C, Schartl M. Production of medakafish chimeras from a stable embryonic stem cell line. Proc Natl Acad Sci 1998; 95:3679–84.
Bejar J, Hong Y, Schartl M. Mitf expression is sufficient to direct differentiation of medaka blastula derived stem cells to melanocytes. Development 2003; 130:6545–53.
Del Bene F, Tessmar-Raible K, Wittbrodt J. Direct interaction of geminin and Six3 in eye development. Nature 2004; 427:745–49.
Nanda I, Kondo M, Hornung U et al. A duplicated copy of DMRT1 in the sex-determining region of the Y chromosome of the medaka, Oryzias latipes. Proc Natl Acad Sci 2002; 99:11778–83.
Schartl M. A comparative view on sex determination in medaka. Mech Dev 2004; 121:639–45.
Elmasri H, Winkler C, Liedtke D et al. Mutations affecting somite formation in the medaka (Oryzias latipes). Mech Dev 2004; 121:659–71.
Elmasri H, Liedtke D, Lücking G et al. her7 and hey1, but not lunatic fringe show dynamic expression during somitogenesis in Medaka (Oryzias latipes). Gene Expression Pattern 2004; 4:553–9.
Gajewski M, Elmasri H, Girschick M et al. Comparative analysis of her genes during fish somitogenesis reveals a mouse/chick-like mode of oscillation in medaka. Development, Genes and Evolution 2006; 216:315–32.
Iwamatsu T. Stages of normal development in the medaka Oryzias latipes. Mech Dev 2004; 121:605–18.
Kimmel CB, Ballard WW, Kimmel SR et al. Stages of embryonic development of the zebrafish. Dev Dyn 1995; 203:253–310.
Dale JK, Maroto M, Dequeant ML et al. Periodic notch inhibition by lunatic fringe underlies the chick segmentation clock. Nature 2003; 421:275–8.
Serth K, Schuster-Gossler K, Cordes R et al. Transcriptional oscillation of lunatic fringe is essential for somitogenesis. Genes Dev 2003; 17:912–25.
Leve C, Gajewski M, Rohr KB et al. Homologues of c-hairy1 (her9) and lunatic fringe in zebrafish are expressed in the developing central nervous system, but not in the presomitic mesoderm. Dev Genes Evol 2001; 211:493–500.
Prince VE, Holley SA, Bally-Cuif L et al. Zebrafish lunatic fringe demarcates segmental boundaries. Mech Dev 2001; 105:175–80.
Leimeister C, Dale K, Fischer A et al. Oscillating expression of c-hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial signaling through multiple interacting bHLH factors. Dev Biol 2000; 227:91–103.
Winkler C, Schäfer M, Duschl J et al. Functional divergence of two zebrafish midkine growth factors following fish-specific gene duplication. Genome Res 2003; 13:1067–81.
Amores A, Suzuki T, Yan YL et al. Developmental roles of pufferfish hox clusters and genome evolution in ray-fin fish. Genome Res 2004; 14:1–10.
Naruse K, Tanaka M, Mita K et al. A medaka gene map: the trace of ancestral vertebrate proto-chromosomes revealed by comparative gene mapping. Genome Res 2004; 14:820–8.
Furutani-Seiki M, Sasado T, Morinaga C et al. A systematic genome-wide screen for mutations affecting organogenesis in Medaka, Oryzias latipes. Mech Dev 2004; 121:647–58.
Hrabe de Angelis M, McIntyre J 2nd, Gossler A. Maintenance of somite borders in mice requires the Delta homologue DIII. Nature 1997; 386:717–21.
Evrard YA, Lun Y, Aulehla A et al. Lunatic fringe is an essential mediator of somite segmentation and patterning. Nature 1998; 394:377–81.
Bessho Y, Sakata R, Komatsu S et al. Dynamic expression and essential functions of Hes7 in somite segmentation. Genes Dev 2001; 15:2642–7.
Carl M, Wittbrodt J. Graded interference with FGF signalling reveals its dorsoventral asymmetry at the mid-hindbrain boundary. Development 1999; 126:5659–67.
Aoyama H, Asamoto K. Determination of somite cells: independence of cell differentiation and morphogenesis. Development 1988; 104:15–28.
Takahashi Y, Inoue T, Gossler A et al. Feedback loops comprising Dll1, Dll3 and Mesp2 and differential involvement of Psen1 are essential for rostrocaudal patterning of somites. Development 2003; 130:4259–68.
Takahashi Y, Kitajima S, Inoue T et al. Differential contributions of Mesp1 and Mesp2 to the epithelialization and rostro-caudal patterning of somites. Development 2005; 132:787–96.
Takahashi Y, Koizumi K, Takagi A et al. Mesp2 initiates somite segmentation through the Notch signalling pathway. Nat Genet 2000; 25:390–6.
Amsterdam A, Hopkins, N. Retroviral-mediated insertional mutagenesis in zebrafish. Methods Cell Biol 2004; 77:3–20.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Landes Bioscience and Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Winkler, C., Elmasri, H. (2008). Genetic Analysis of Somite Formation in Laboratory Fish Models. In: Maroto, M., Whittock, N.V. (eds) Somitogenesis. Advances in Experimental Medicine and Biology, vol 638. Springer, New York, NY. https://doi.org/10.1007/978-0-387-09606-3_3
Download citation
DOI: https://doi.org/10.1007/978-0-387-09606-3_3
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-09605-6
Online ISBN: 978-0-387-09606-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)