Zebrafish Development

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Zebrafish or zebra danio (danio rerio) are seen as the latest "model' for embryological development studies. These embryos have the great advantage that they develop as "see through" embryos, that is, all internal development can be clearly observed from the outside in the living embryo. Much of the early modern work using this embryo model began with the papers of Kimmel.[1][2]

Several large laboratories in the US are now developing large breeding programs to carry out "knockouts" and to find spontaneous mutants of interest.

Fish Links: Zebrafish Development | Medaka Development | Salmon Development | Movie - Zebrafish Heart | Student Group Project - Zebrafish | Recent References | Category:Zebrafish | Category:Medaka

Some Recent Findings

Nipbl heart and organ patterning[3]
  • Construction of a vertebrate embryo from two opposing morphogen gradients[4] "Here, we show that opposing gradients of bone morphogenetic protein (BMP) and Nodal, two transforming growth factor family members that act as morphogens, are sufficient to induce molecular and cellular mechanisms required to organize, in vivo or in vitro, uncommitted cells of the zebrafish blastula animal pole into a well-developed embryo." BMP
  • FishFace: interactive atlas of zebrafish craniofacial development at cellular resolution[5] "We present the Fish Face Atlas, an online, 3D-interactive atlas of craniofacial development in the zebrafish Danio rerio. Alizarin red-stained skulls scanned by fluorescent optical projection tomography and segmented into individual elements provide a resource for understanding the 3D structure of the zebrafish craniofacial skeleton." See also Online Zebrafish Atlases
  • Multifactorial Origins of Heart and Gut Defects in nipbl-Deficient Zebrafish, a Model of Cornelia de Lange Syndrome[3] "Cornelia de Lange Syndrome (CdLS) is the founding member of a class of multi-organ system birth defect syndromes termed cohesinopathies, named for the chromatin-associated protein complex cohesin, which mediates sister chromatid cohesion. Most cases of CdLS are caused by haploinsufficiency for Nipped-B-like (Nipbl), a highly conserved protein that facilitates cohesin loading. ... These findings support the view that birth defects in CdLS arise from collective effects of quantitative changes in gene expression. Interestingly, both the phenotypes and gene expression changes in nipbl morphants differed from those in mutants or morphants for genes encoding cohesin subunits, suggesting that the transcriptional functions of Nipbl cannot be ascribed simply to its role in cohesin loading. (OMIM - CDLS1 | CDLS2 | CDLS3)
  • The zebrafish transcriptome during early development[6] "The three earliest developmental stages were similar when comparing highly expressed genes, whereas the 50% epiboly stage differed from the other three stages in the identity of highly expressed genes, number of uniquely expressed genes and enrichment of GO molecular functions. Taken together, these observations indicate a major transition in gene regulation and transcriptional activity taking place between the 512-cell and 50% epiboly stages, in accordance with previous studies."
  • Genetic analysis of fin development in zebrafish identifies furin and hemicentin1 as potential novel fraser syndrome disease genes[7] " Three of them are due to mutations in zebrafish orthologues of FRAS1, FREM1, or FREM2, large basement membrane protein encoding genes that are mutated in mouse bleb mutants and in human patients suffering from Fraser Syndrome, a rare congenital condition characterized by syndactyly and cryptophthalmos. Fin blistering in a fourth group of zebrafish mutants is caused by mutations in Hemicentin1 (Hmcn1), another large extracellular matrix protein the function of which in vertebrates was hitherto unknown. Our mutant and dose-dependent interaction data suggest a potential involvement of Hmcn1 in Fraser complex-dependent basement membrane anchorage. Furthermore, we present biochemical and genetic data suggesting a role for the proprotein convertase FurinA in zebrafish fin development and cell surface shedding of Fras1 and Frem2, thereby allowing proper localization of the proteins within the basement membrane of forming fins."
More recent papers
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This table shows an automated computer PubMed search using the listed sub-heading term.
  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches

Search term: Zebrafish Embryology

Anne Guimier, George C Gabriel, Fanny Bajolle, Michael Tsang, Hui Liu, Aaron Noll, Molly Schwartz, Rajae El Malti, Laurie D Smith, Nikolai T Klena, Gina Jimenez, Neil A Miller, Myriam Oufadem, Anne Moreau de Bellaing, Hisato Yagi, Carol J Saunders, Candice N Baker, Sylvie Di Filippo, Kevin A Peterson, Isabelle Thiffault, Christine Bole-Feysot, Linda D Cooley, Emily G Farrow, Cécile Masson, Patric Schoen, Jean-François Deleuze, Patrick Nitschké, Stanislas Lyonnet, Loic de Pontual, Stephen A Murray, Damien Bonnet, Stephen F Kingsmore, Jeanne Amiel, Patrice Bouvagnet, Cecilia W Lo, Christopher T Gordon MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates. Nat. Genet.: 2015; PubMed 26437028

Ronen Durst, Kimberly Sauls, David S Peal, Annemarieke deVlaming, Katelynn Toomer, Maire Leyne, Monica Salani, Michael E Talkowski, Harrison Brand, Maëlle Perrocheau, Charles Simpson, Christopher Jett, Matthew R Stone, Florie Charles, Colby Chiang, Stacey N Lynch, Nabila Bouatia-Naji, Francesca N Delling, Lisa A Freed, Christophe Tribouilloy, Thierry Le Tourneau, Hervé LeMarec, Leticia Fernandez-Friera, Jorge Solis, Daniel Trujillano, Stephan Ossowski, Xavier Estivill, Christian Dina, Patrick Bruneval, Adrian Chester, Jean-Jacques Schott, Kenneth D Irvine, Yaopan Mao, Andy Wessels, Tahirali Motiwala, Michel Puceat, Yoshikazu Tsukasaki, Donald R Menick, Harinath Kasiganesan, Xingju Nie, Ann-Marie Broome, Katherine Williams, Amanda Johnson, Roger R Markwald, Xavier Jeunemaitre, Albert Hagege, Robert A Levine, David J Milan, Russell A Norris, Susan A Slaugenhaupt Mutations in DCHS1 cause mitral valve prolapse. Nature: 2015; PubMed 26258302

Ana Luzio, Sandra M Monteiro, Sofia Garcia-Santos, Eduardo Rocha, António A Fontaínhas-Fernandes, Ana M Coimbra Zebrafish sex differentiation and gonad development after exposure to 17α-ethinylestradiol, fadrozole and their binary mixture: A stereological study. Aquat. Toxicol.: 2015, 166;83-95 PubMed 26240953

Wei Shi, Fen Wang, Ming Gao, Yang Yang, Zhaoxia Du, Chen Wang, Yao Yao, Kun He, Xueran Chen, Aijun Hao ZDHHC17 promotes axon outgrowth by regulating TrkA-tubulin complex formation. Mol. Cell. Neurosci.: 2015; PubMed 26232532

Rebecca Greenlees, Marija Mihelec, Saira Yousoof, Daniel Speidel, Selwin K Wu, Silke Rinkwitz, Ivan Prokudin, Rahat Perveen, Anson Cheng, Alan Ma, Benjamin Nash, Rachel Gillespie, David A F Loebel, Jill Clayton-Smith, I Christopher Lloyd, John R Grigg, Patrick P L Tam, Alpha S Yap, Thomas S Becker, Graeme C M Black, Elena Semina, Robyn V Jamieson Mutations in SIPA1L3 cause eye defects through disruption of cell polarity and cytoskeleton organization. Hum. Mol. Genet.: 2015; PubMed 26231217


Movie of an immobilized zebrafish embryo development from the 1-cell stage to 85 hours post fertilisation (hpf).[8]

Zebrafish 01 icon.jpg
 ‎‎Zebrafish Embryo
Page | Play

Timeline and Stages of Embryonic Development

Duration Period Name Image
0 - 0.75 hrs Zygote Period The Zygote Period. Photo supplied by Judy Cebra-Thomas
0.75 - 2.25 hrs Cleavage Period The Cleavage Period. Photo supplied by Judy Cebra-Thomas
2.25 - 5.25 hrs Blastula Period The Blastula Period. Photo supplied by Judy Cebra-Thomas‎
5.25 - 10.33 hrs Gastrula Period The Gastrula Period. Photo supplied by Judy Cebra-Thomas
10.33 - 24 hrs Segmentation Period The Segmentation Period. Photo supplied by Judy Cebra-Thomas
24 - 48 hrs Pharyngula Period The Pharyngula Period. Photo supplied by Judy Cebra-Thomas
48-72 hrs Hatching Period The Hatching Period. Photo supplied by Judy Cebra-Thomas‎
72 hrs - 30 Days Larval Period The Larval Period. Photo supplied by Judy Cebra-Thomas‎

Pharyngula Period

  • Transition from Prim 5 to Long-pec
  • The body axis begins to straighten and the head straightens out and lifts dorsally
  • Notochord is well developed
  • Formation of the Dorsal and Ventral Stripe
  • Nervous system is hollow and expanding anteriorly
  • The brain has developed into 5 distinct lobes
  • Seven pharyngeal arch's develop rapidly during this stage
  • Pectoral fins begin to develop
  • The Circulatory system develops and the heart beats for the first time
  • Blood begins to circulate through a closed circuit of channels
  • Tactile sensitivity appears and uncoordinated movements occur


Zebrafish skull neural crest.jpg Zebrafish Skull Neural Crest Contribution[9]

Diagrams depict the cartilage elements and bones that are NC-derived (green), and those that show no evidence of NC contribution, and are presumably derived from mesoderm (magenta).

  • Top - shows a dorsal view of the chondrocranium from an approximately 12 dpf larva.
  • Second - side view of the bones of an adult skull, with some elements of the pectoral girdle also shown.
  • Third - a dorsal view of the dorsal aspect of the adult skull.
  • Bottom - view is of the base of the neurocranium, with the pharyngeal skeleton removed.

(text modified from figure legend)

Links: Neural Crest Development | Skull Development


Fibroblast Growth Factor

  • Fgf8 and Fgf3 - regulating the segmentation of the pharyngeal endoderm into pouches. [10]
  • Fgf24 and Fgf8 - promotes posterior mesodermal development.[11]

  • Sox9 - required for cartilage morphogenesis.[12]


  1. C B Kimmel, S K Sessions, R J Kimmel Morphogenesis and synaptogenesis of the zebrafish Mauthner neuron. J. Comp. Neurol.: 1981, 198(1);101-20 PubMed 7229136
  2. C B Kimmel, D S Sepich, B Trevarrow Development of segmentation in zebrafish. Development: 1988, 104 Suppl;197-207 PubMed 3077108
  3. 3.0 3.1 Akihiko Muto, Anne L Calof, Arthur D Lander, Thomas F Schilling Multifactorial origins of heart and gut defects in nipbl-deficient zebrafish, a model of Cornelia de Lange Syndrome. PLoS Biol.: 2011, 9(10);e1001181 PubMed 22039349
  4. Peng-Fei Xu, Nathalie Houssin, Karine F Ferri-Lagneau, Bernard Thisse, Christine Thisse Construction of a vertebrate embryo from two opposing morphogen gradients. Science: 2014, 344(6179);87-9 PubMed 24700857
  5. B Frank Eames, April DeLaurier, Bonnie Ullmann, Tyler R Huycke, James T Nichols, John Dowd, Marcie McFadden, Mark M Sasaki, Charles B Kimmel FishFace: interactive atlas of zebrafish craniofacial development at cellular resolution. BMC Dev. Biol.: 2013, 13;23 PubMed 23714426
  6. Liselotte Vesterlund, Hong Jiao, Per Unneberg, Outi Hovatta, Juha Kere The zebrafish transcriptome during early development. BMC Dev. Biol.: 2011, 11;30 PubMed 21609443
  7. Thomas J Carney, Natália Martins Feitosa, Carmen Sonntag, Krasimir Slanchev, Johannes Kluger, Daiji Kiyozumi, Jan M Gebauer, Jared Coffin Talbot, Charles B Kimmel, Kiyotoshi Sekiguchi, Raimund Wagener, Heinz Schwarz, Phillip W Ingham, Matthias Hammerschmidt Genetic analysis of fin development in zebrafish identifies furin and hemicentin1 as potential novel fraser syndrome disease genes. PLoS Genet.: 2010, 6(4);e1000907 PubMed 20419147
  8. Ian A Swinburne, Kishore R Mosaliganti, Amelia A Green, Sean G Megason Improved Long-Term Imaging of Embryos with Genetically Encoded α-Bungarotoxin. PLoS ONE: 2015, 10(8);e0134005 PubMed 26244658 | PLoS One.
  9. Kague E, Gallagher M, Burke S, Parsons M, Franz-Odendaal T, et al. (2012) Skeletogenic Fate of Zebrafish Cranial and Trunk Neural Crest. PLoS ONE 7(11): e47394. doi:10.1371/journal.pone.0047394 PLoS ONE
  10. Justin Gage Crump, Lisa Maves, Nathan D Lawson, Brant M Weinstein, Charles B Kimmel An essential role for Fgfs in endodermal pouch formation influences later craniofacial skeletal patterning. Development: 2004, 131(22);5703-16 PubMed 15509770
  11. Bruce W Draper, David W Stock, Charles B Kimmel Zebrafish fgf24 functions with fgf8 to promote posterior mesodermal development. Development: 2003, 130(19);4639-54 PubMed 12925590
  12. Yi-Lin Yan, Craig T Miller, Robert M Nissen, Amy Singer, Dong Liu, Anette Kirn, Bruce Draper, John Willoughby, Paul A Morcos, Adam Amsterdam, Bon-Chu Chung, Monte Westerfield, Pascal Haffter, Nancy Hopkins, Charles Kimmel, John H Postlethwait, Robert Nissen A zebrafish sox9 gene required for cartilage morphogenesis. Development: 2002, 129(21);5065-79 PubMed 12397114


Zebrafish "is the only peer-reviewed journal to focus on the zebrafish, which has numerous valuable features as a model organism for the study of vertebrate development. Due to its prolific reproduction and the external development of the transparent embryo, the zebrafish is a prime model for genetic and developmental studies, as well as research in toxicology and genomics. While genetically more distant from humans, the vertebrate zebrafish nevertheless has comparable organs and tissues, such as heart, kidney, pancreas, bones, and cartilage." [jour PubMed listing]


Willy Supatto, Julien Vermot From cilia hydrodynamics to zebrafish embryonic development. Curr. Top. Dev. Biol.: 2011, 95;33-66 PubMed 21501748

Lara Carvalho, Carl-Philipp Heisenberg The yolk syncytial layer in early zebrafish development. Trends Cell Biol.: 2010, 20(10);586-92 PubMed 20674361

Sebastiaan A Brittijn, Suzanne J Duivesteijn, Mounia Belmamoune, Laura F M Bertens, Wilbert Bitter, Joost D de Bruijn, Danielle L Champagne, Edwin Cuppen, Gert Flik, Christina M Vandenbroucke-Grauls, Richard A J Janssen, Ilse M L de Jong, Edo Ronald de Kloet, Alexander Kros, Annemarie H Meijer, Juriaan R Metz, Astrid M van der Sar, Marcel J M Schaaf, Stefan Schulte-Merker, Herman P Spaink, Paul P Tak, Fons J Verbeek, Margriet J Vervoordeldonk, Freek J Vonk, Frans Witte, Huipin Yuan, Michael K Richardson Zebrafish development and regeneration: new tools for biomedical research. Int. J. Dev. Biol.: 2009, 53(5-6);835-50 PubMed 19557689

Jeroen Bakkers, Manon C Verhoeven, Salim Abdelilah-Seyfried Shaping the zebrafish heart: from left-right axis specification to epithelial tissue morphogenesis. Dev. Biol.: 2009, 330(2);213-20 PubMed 19371733

Tzu-Min Chan, William Longabaugh, Hamid Bolouri, Hua-Ling Chen, Wen-Fang Tseng, Chung-Hao Chao, Te-Hsuan Jang, Yu-I Lin, Shao-Chin Hung, Horng-Dar Wang, Chiou-Hwa Yuh Developmental gene regulatory networks in the zebrafish embryo. Biochim. Biophys. Acta: 2009, 1789(4);279-98 PubMed 18992377


Search Pubmed

Search Pubmed: Zebrafish Development

Additional Images


  • deep cell layer - (DEL) formed after blastula stage that forms the three germ layers (ectoderm, mesoderm, and endoderm).
  • epiboly - (Greek, "epibol" = a throwing or laying on) Term describing the division and movement of ectodermal cells during gastrulation, thinning and spreading this layer to cover the whole of the embryo. Cellular movements are thought to occur in all vertebrates, but have been most clearly identified in both the zebrafish and frog (xenopus laevis).
  • enveloping layer - (EVL) an epithelial monolayer formed after blastula stage that undergoes epiboly.
  • Kupffer's vesicle - (ciliated organ of asymmetry, primitive node) a transient epithelial fluid-filled sac located midventrally posterior to the yolk cell or its extension. The vesicle has been described as equivalent to the primitive node for establishing embryo left-right (L-R) axis. PMID 21876750
  • yolk syncytial layer - (YSL) membrane-enclosed group of nuclei that lie on top of the yolk cell formed after blastula stage that undergoes epiboly.

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name.

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Cite this page: Hill, M.A. (2015) Embryology Zebrafish Development. Retrieved October 10, 2015, from https://embryology.med.unsw.edu.au/embryology/index.php/Zebrafish_Development

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© Dr Mark Hill 2015, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G