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]
  • A crystal-clear zebrafish for in vivo imaging[4] "Here we present crystal, an optically clear zebrafish mutant obtained by combining different viable mutations affecting skin pigmentation. Compared to the previously described combinatorial mutant casper, the crystal mutant lacks pigmentation also in the retinal pigment epithelium, therefore enabling optical access to the eyes. Unlike PTU-treated animals, crystal larvae are able to perform visually guided behaviours, such as the optomotor response, as efficiently as wild type larvae. To validate the in vivo application of crystal larvae, we performed whole-brain light-sheet imaging and two-photon calcium imaging of neural activity in the retina."
  • Construction of a vertebrate embryo from two opposing morphogen gradients[5] "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[6] "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[7] "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[8] " 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

Seth M Weinberg, Robert Cornell, Elizabeth J Leslie Craniofacial genetics: Where have we been and where are we going? PLoS Genet.: 2018, 14(6);e1007438 PubMed 29927928

Shuhui Zhang, Xiaodong Liu, Mingzhu Sun, Qiuping Zhang, Teng Li, Xiang Li, Jia Xu, Xin Zhao, Dongyan Chen, Xizeng Feng Reversal of reserpine-induced depression and cognitive disorder in zebrafish by sertraline and Traditional Chinese Medicine (TCM). Behav Brain Funct: 2018, 14(1);13 PubMed 29898741

Jiamiao Hu, Shaoling Lin, Jim Junhui Huang, Peter C K Cheung Mechanistic study of the in vitro and in vivo inhibitory effects of protocatechuic acid and syringic acid on VEGF-induced angiogenesis. J. Agric. Food Chem.: 2018; PubMed 29886729

Yan M Zhang, Milena A Zimmer, Talia Guardia, Scott J Callahan, Chandrani Mondal, Julie Di Martino, Toshimitsu Takagi, Myles Fennell, Ralph Garippa, Nathaniel R Campbell, Jose Javier Bravo-Cordero, Richard M White Distant Insulin Signaling Regulates Vertebrate Pigmentation through the Sheddase Bace2. Dev. Cell: 2018; PubMed 29804876

Cassidy S Bernstein, Mitchell T Anderson, Chintan Gohel, Kayleigh Slater, Jeffrey M Gross, Seema Agarwala The Cellular Bases of Choroid Fissure Formation and Closure. Dev. Biol.: 2018; PubMed 29803644


Movie of an immobilized zebrafish embryo development from the 1-cell stage to 85 hours post fertilisation (hpf).[9]

Zebrafish 01 icon.jpg
 ‎‎Zebrafish Embryo
Page | Play


Zebrafish Stages

Zebrafish Stages
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
Links: zebrafish | zebrafish timeline
Timeline Links: human timeline | mouse timeline | mouse detailed timeline | chicken timeline | rat timeline | zebrafish timeline | Medaka | comparative | Category:Timeline
Human Trimesters - Systems  
Period: first trimester timeline | second trimester timeline | third trimester timeline

Systems: bone timeline | eye neural crest timeline | heart abnormality timeline | hearing timeline | hearing EAM timeline | muscle timeline | ovary timeline | pelvis timeline | placental villi timeline | shoulder timeline | smell timeline | spleen timeline | ventricular timeline

upper limb ossification timeline | lower limb ossification timeline | 1932 Guinea pig day 11-21 | 1933 Guinea pig day 21-35
Embryology History: 1600-1699 | 1700-1799 | 1800-1899 | 1900-1909 | 1910-1919 | 1920-1929 | 1930-1939 | 1940-1949 | 1950-1959 | 1960-1969 | 1970-1979 | 1980-1989 | 1990-1999 | Historic Papers | Embryologists

Image Source: Image kindly contributed by Dr Judith Cebra-Thomas Department of Biology, Millersville University. From her Lab Protocols showing Zebrafish Stages sequence based on previously published sources including; Kimmel CB, Ballard WW, Kimmel SR, Ullmann B & Schilling TF. (1995). Stages of embryonic development of the zebrafish. Dev. Dyn. , 203, 253-310. PMID: 8589427 DOI.

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 [10]

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



Lateral line is a zebrafish sensory system, used to detect changes in water flow, composed of clusters of mechanosensory hair cells called neuromasts.


Fibroblast Growth Factor

  • Fgf8 and Fgf3 - regulating the segmentation of the pharyngeal endoderm into pouches.[11]
  • Fgf24 and Fgf8 - promotes posterior mesodermal development.[12]

  • Sox9 - required for cartilage morphogenesis.[13]


  1. Kimmel CB, Sessions SK & Kimmel RJ. (1981). Morphogenesis and synaptogenesis of the zebrafish Mauthner neuron. J. Comp. Neurol. , 198, 101-20. PMID: 7229136 DOI.
  2. Kimmel CB, Sepich DS & Trevarrow B. (1988). Development of segmentation in zebrafish. Development , 104 Suppl, 197-207. PMID: 3077108
  3. 3.0 3.1 Muto A, Calof AL, Lander AD & Schilling TF. (2011). Multifactorial origins of heart and gut defects in nipbl-deficient zebrafish, a model of Cornelia de Lange Syndrome. PLoS Biol. , 9, e1001181. PMID: 22039349 DOI.
  4. Antinucci P & Hindges R. (2016). A crystal-clear zebrafish for in vivo imaging. Sci Rep , 6, 29490. PMID: 27381182 DOI.
  5. Xu PF, Houssin N, Ferri-Lagneau KF, Thisse B & Thisse C. (2014). Construction of a vertebrate embryo from two opposing morphogen gradients. Science , 344, 87-9. PMID: 24700857 DOI.
  6. Eames BF, DeLaurier A, Ullmann B, Huycke TR, Nichols JT, Dowd J, McFadden M, Sasaki MM & Kimmel CB. (2013). FishFace: interactive atlas of zebrafish craniofacial development at cellular resolution. BMC Dev. Biol. , 13, 23. PMID: 23714426 DOI.
  7. Vesterlund L, Jiao H, Unneberg P, Hovatta O & Kere J. (2011). The zebrafish transcriptome during early development. BMC Dev. Biol. , 11, 30. PMID: 21609443 DOI.
  8. Carney TJ, Feitosa NM, Sonntag C, Slanchev K, Kluger J, Kiyozumi D, Gebauer JM, Coffin Talbot J, Kimmel CB, Sekiguchi K, Wagener R, Schwarz H, Ingham PW & Hammerschmidt M. (2010). Genetic analysis of fin development in zebrafish identifies furin and hemicentin1 as potential novel fraser syndrome disease genes. PLoS Genet. , 6, e1000907. PMID: 20419147 DOI.
  9. Swinburne IA, Mosaliganti KR, Green AA & Megason SG. (2015). Improved Long-Term Imaging of Embryos with Genetically Encoded α-Bungarotoxin. PLoS ONE , 10, e0134005. PMID: 26244658 DOI.
  10. Kague E, Gallagher M, Burke S, Parsons M, Franz-Odendaal T & Fisher S. (2012). Skeletogenic fate of zebrafish cranial and trunk neural crest. PLoS ONE , 7, e47394. PMID: 23155370 DOI.
  11. Crump JG, Maves L, Lawson ND, Weinstein BM & Kimmel CB. (2004). An essential role for Fgfs in endodermal pouch formation influences later craniofacial skeletal patterning. Development , 131, 5703-16. PMID: 15509770 DOI.
  12. Draper BW, Stock DW & Kimmel CB. (2003). Zebrafish fgf24 functions with fgf8 to promote posterior mesodermal development. Development , 130, 4639-54. PMID: 12925590 DOI.
  13. Yan YL, Miller CT, Nissen RM, Singer A, Liu D, Kirn A, Draper B, Willoughby J, Morcos PA, Amsterdam A, Chung BC, Westerfield M, Haffter P, Hopkins N, Kimmel C, Postlethwait JH & Nissen R. (2002). A zebrafish sox9 gene required for cartilage morphogenesis. Development , 129, 5065-79. PMID: 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.

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Cite this page: Hill, M.A. (2018, July 20) Embryology Zebrafish Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Zebrafish_Development

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