Epiboly

Epiboly in zebrafish is the first coordinated cell movement, beginning at the dome stage late in the blastula period and continuing throughout gastrulation.{{cite journal |vauthors=Warga RM, Kimmel CB |title=Cell movements during epiboly and gastrulation in zebrafish |journal=Development |volume=108 |issue=4 |pages=569–80 |date=April 1990 |doi=10.1242/dev.108.4.569 |pmid=2387236 |url=http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=2387236|url-access=subscription }} At this point the zebrafish embryo contains three portions: an epithelial monolayer known as the enveloping layer (EVL), a yolk syncytial layer (YSL) which is a membrane-enclosed group of nuclei that lie on top of the yolk cell, and the deep cells (DEL) of the blastoderm which will eventually form the embryo's three germ layers (ectoderm, mesoderm, and endoderm). The EVL, YSL, and DEL all undergo epiboly.

File:Epiboly process in zebra fish svg hariadhi.svg

File:Midblastula embryo svg hariadhi.svg

Radial intercalation occurs in the DEL. Interior cells of the blastoderm move towards the outer cells, thus "intercalating" with each other. The blastoderm begins to thin as it spreads toward the vegetal pole of the embryo until it has completely engulfed the yolk cell.{{cite journal |author1=Donald A. Kane |author2=Karen N. McFarland |author3=Rachel M. Warga |date=2005-03-01 |title=Mutations in half baked/E-cadherin block cell behaviors that are necessary for teleost epiboly |journal=Development |volume=132 |issue=5 |pages=1105–16 |pmid=15689372 |doi=10.1242/dev.01668 |doi-access=free }} The EVL also moves vegetally during epiboly, increasing its surface area as it spreads. Work in the ray-finned fish fundulus has shown that no large rearrangements occur in the EVL; instead, cells at the leading edge of the EVL align and constrict.{{cite journal |vauthors=Kimmel CB, Warga RM |title=Indeterminate cell lineage of the zebrafish embryo |journal=Dev. Biol. |volume=124 |issue=1 |pages=269–80 |date=November 1987 |pmid=3666309 |doi=10.1016/0012-1606(87)90478-7}}{{cite journal |author1=C.B. Kimmel |author2=R.M. Warga |author3=T.F. Schilling |date=1990-04-01 |title=Origin and organization of the zebrafish fate map |journal=Development |volume=108 |issue=4 |pages=581–94 |doi=10.1242/dev.108.4.581 |pmid=2387237 |url=http://dev.biologists.org/content/108/4/581.long |url-access=subscription }} The YSL also moves towards the vegetal pole, spreading along the surface of the yolk and migrating slightly ahead of the blastomeres.{{cite journal |vauthors=D'Amico LA, Cooper MS |title=Morphogenetic domains in the yolk syncytial layer of axiating zebrafish embryos |journal=Dev. Dyn. |volume=222 |issue=4 |pages=611–24 |date=December 2001 |pmid=11748830 |doi=10.1002/dvdy.1216 |s2cid=41436032 |url=http://www3.interscience.wiley.com/journal/87510562/abstract|archive-url=https://archive.today/20130105161140/http://www3.interscience.wiley.com/journal/87510562/abstract|url-status=dead|archive-date=2013-01-05}} Once epiboly is complete, the DEL, EVL, and YSL have engulfed the yolk cell, forming a closure known as the blastopore.

Completion of epiboly requires the coordination of cytoskeletal changes across the embryo. The YSL appears to play a prominent role in this process. Studies on fundulus demonstrated that the YSL is capable of undergoing epiboly even when the blastoderm has been removed, however, the blastoderm cannot undergo epiboly in the absence of the YSL.{{cite journal |vauthors=Betchaku T, Trinkaus JP |title=Contact relations, surface activity, and cortical microfilaments of marginal cells of the enveloping layer and of the yolk syncytial and yolk cytoplasmic layers of fundulus before and during epiboly |journal=J. Exp. Zool. |volume=206 |issue=3 |pages=381–426 |date=December 1978 |pmid=568653 |doi=10.1002/jez.1402060310 }} In zebrafish, there is a microtubule array in the yolk that extends from the animal to the vegetal pole of the embryo, and that contracts as epiboly progresses.{{cite journal |author1=L. Solnica-Krezel |author2=W. Driever |date=1994-09-01 |title=Microtubule arrays of the zebrafish yolk cell: organization and function during epiboly |journal=Development |volume=120 |issue=9 |pages=2443–55 |doi=10.1242/dev.120.9.2443 |pmid=7956824 |url=http://dev.biologists.org/content/120/9/2443.long|url-access=subscription }} Treating embryos with the microtubule depolymerizing agent nocodazole completely blocks epiboly of the YSL and partially blocks epiboly of the blastoderm, while treating with the microtubule stabilizing agent taxol blocks epiboly of all cell layers. There is also evidence for the importance of actin-based structures in epiboly. Ring-like structures of filamentous actin have been observed at the leading edge of the enveloping layer, where it contacts the yolk cell.{{cite journal |doi= 10.1002/dvdy.20144 |vauthors=Cheng JC, Miller AL, Webb SE |date=October 2004 |title= Organization and function of microfilaments during late epiboly in zebrafish embryos|journal=Dev. Dyn. |volume=231 |issue=2 |pages=313–23|pmid=15366008 |doi-access=free }} It is thought that a network of filamentous actin in the yolk might constrict in a myosin-II dependent manner to close the blastopore at the end of epiboly, via a "purse-string mechanism".{{cite journal |author1=Mathias Köppen |author2=Beatriz García Fernández |author3=Lara Carvalho |author4=Antonio Jacinto |author5=Carl-Philipp Heisenberg |date=2006-07-15 |title=Coordinated cell-shape changes control epithelial movement in zebrafish and Drosophila |journal=Development |volume=133 |issue=14 |pages=2671–81 |pmid=16794032 |doi=10.1242/dev.02439 |doi-access=free }} Treating embryos with the actin destabilizer cytochalasin b results in delayed or arrested epiboly.

There is still debate on the extent to which the DEL and EVL epibolic movements are active movements.A. Bruce and R. Winklbauer 03-P005 Zebra fish epiboly as a model of vertebrate cell rearrangement, Mechanisms of Development 126 (2009) The EVL contacts the YSL by means of tight junctions. It is thought that these contacts allow the YSL to "tow" the EVL towards the vegetal pole. Claudin E is a molecule found in tight junctions that appears to be expressed in the EVL and required for normal zebrafish epiboly, supporting this hypothesis.{{cite journal |vauthors=Siddiqui M, Sheikh H, Tran C, Bruce A |title=The tight junction component claudin E is required for zebra fish epiboly |journal=Developmental Dynamics |volume=239 |issue= 2|pages= 715–722|year=2010 |doi=10.1002/dvdy.22172 |pmid=20014098 |url=http://www3.interscience.wiley.com/cgi-bin/fulltext/123210817/PDFSTART|doi-access=free|url-access=subscription}}{{dead link|date=February 2019|bot=medic}}{{cbignore|bot=medic}} Additionally, zebrafish embryos that fail to make a fully differentiated EVL show defects in epibolic movements of the DEL, EVL, and YSL, suggesting a requirement for a normal EVL for the epiboly of all three cell layers.{{Cite journal|vauthors=Fukazawa C, Santiago C, Park K, Deery W, Gomez de la Torre Canny S, Holterhoff C, Wagner DS | title = poky/chuk/ikk1 is required for differentiation of the zebrafish embryonic epidermis | journal = Developmental Biology | volume = 346 | issue = 2 | pages = 272–83 |date=October 2010 | pmid = 20692251 | pmc = 2956273 | doi = 10.1016/j.ydbio.2010.07.037 }}

The cell-cell adhesion molecule E-cadherin has been shown to be required for the radial intercalation of the deep cells. Many other molecules involved in cell-cell contact are implicated in zebrafish epiboly, including G alpha (12/13) which interacts with E-cadherin and actin, as well as the cell adhesion molecule EpCam in the EVL, which may modulate adhesion with the underlying deep cells.{{cite journal |author1=Fang Lin |author2=Songhai Chen |author3=Diane S. Sepich |author4=Jennifer Ray Panizzi |author5=Sherry G. Clendenon |author6=James A. Marrs |author7=Heidi E. Hamm |date=2009-03-23 |title=Gα12/13 regulate epiboly by inhibiting E-cadherin activity and modulating the actin cytoskeleton |journal=The Journal of Cell Biology |volume=184 |issue=6 |pages=909–21 |pmid=19307601 |doi=10.1083/jcb.200805148 |last8=Solnica-Krezel |first8=L. |pmc=2664974 }}{{cite journal |author=Slanchev K |title=The Epithelial Cell Adhesion Molecule EpCAM Is Required for Epithelial Morphogenesis and Integrity during Zebrafish Epiboly and Skin Development |journal=PLOS Genet. |volume=5 |issue=7 |pages=e1000563 |date=July 2009 |pmid=19609345 |pmc=2700972 |doi=10.1371/journal.pgen.1000563 |editor1-last=Mullins |editor1-first=Mary C |author2= Carney TJ |author3= Stemmler MP |display-authors=etal |doi-access=free }}

The molecule fibronectin has been found to play a role in radial intercalation.{{cite journal |author1=Mungo Marsden |author2=Douglas W. DeSimone |date=2001-09-15 |title=Regulation of cell polarity, radial intercalation and epiboly in Xenopus: novel roles for integrin and fibronectin |journal=Development |volume=128 |issue=18 |pages=3635–47 |doi=10.1242/dev.128.18.3635 |pmid=11566866 |url=http://dev.biologists.org/content/128/18/3635.full |url-access=subscription }} Other signaling pathways that appear to function in epiboly include the Wnt/PCP pathway,{{cite journal |author1=M. Hammerschmidt |author2=F. Pelegri |author3=M.C. Mullins |author4=D.A. Kane |author5=M. Brand |author6=F.J. van Eeden |author7=M. Furutani-Seiki |date=1996-12-01 |title=Mutations affecting morphogenesis during gastrulation and tail formation in the zebrafish, Danio rerio |journal=Development |volume=123 |issue=1 |pages=143–51 |pmid=9007236 |url=http://dev.biologists.org/content/123/1/143.long |last8=Granato |first8=M |last9=Haffter |first9=P |doi=10.1242/dev.123.1.143 |url-access=subscription }} PDGF-PI3K pathway,{{cite journal |author1=Martina Nagel |author2=Emilios Tahinci |author3=Karen Symes |author4=Rudolf Winklbauer |date=2004-06-01 |title=Guidance of mesoderm cell migration in the Xenopus gastrula requires PDGF signaling |journal=Development |volume=131 |issue=11 |pages=2727–36 |pmid=15128658 |doi=10.1242/dev.01141 |doi-access=free }} Eph-Ephrin signaling,{{cite journal |author=Oates AC |title=An early developmental role for eph-ephrin interaction during vertebrate gastrulation |journal=Mech. Dev. |volume=83 |issue=1–2 |pages=77–94 |date=May 1999 |pmid=10381569 |doi=10.1016/S0925-4773(99)00036-2 |author2= Lackmann M |author3= Power MA |display-authors=etal |doi-access=free }}

JAK-STAT signaling,{{cite journal |vauthors=Conway G, Margoliath A, Wong-Madden S, Roberts RJ, Gilbert W |title=Jak1 kinase is required for cell migrations and anterior specification in zebrafish embryos |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue=7 |pages=3082–7 |date=April 1997 |pmid=9096349 |pmc=20325 |doi=10.1073/pnas.94.7.3082|bibcode=1997PNAS...94.3082C |doi-access=free }} and the MAP kinase cascade.{{cite journal |vauthors=Holloway BA, Gomez de la Torre Canny S, Ye Y, Slusarski DC, Freisinger CM, Dosch R, Chou MM, Wagner DS, Mullins MC |title= A Novel Role for MAPKAPK2 in Morphogenesis during Zebrafish Development|journal= PLOS Genetics |volume=5 |issue=3 |pages=e1000413|date=March 2009 |pmid=19282986 |pmc=2652113 |doi= 10.1371/journal.pgen.1000413 |editor1-last= Barsh |editor1-first= Gregory S.|doi-access= free}}

Epibolic movements have been conserved in vertebrates. Though most work on epiboly has been done in fish, there is also a body of work concerning epiboly in the African clawed frog, Xenopus laevis. Comparisons of epiboly in amniotes, teleosts and X. laevis show that the key movement of epiboly in the fish and frog is radial intercalation while in amniotes it would appear to be cell division in the plane of the epithelium. All groups undergo cell shape changes such as the characteristic flattening of cells to increase surface area.{{cite journal |author=Solnica-Krezel L |title=Conserved patterns of cell movements during vertebrate gastrulation |journal=Curr. Biol. |volume=15 |issue=6 |pages=R213–28 |date=March 2005 |pmid=15797016 |doi=10.1016/j.cub.2005.03.016 |doi-access=free }}

{{Reflist|2}}

• [https://www.researchgate.net/figure/Developmental-mRNA-expression-pattern-of-the-zebrafish-cdx1b-gene-cdx1b-mRNA-was_fig1_5616717 Developmental mRNA expression pattern of the zebrafish cdx1b gene]

Category:Gastrulation