The DVE changes distal epiblast fate from definitive endoderm to neurectoderm by antagonizing nodal signaling.
To assess the function of the distal visceral endoderm (DVE) of embryonic day 5.5 (E5.5) embryos, we established a system to directly ablate the DVE and observe the consequences after culture. When the DVE was successfully ablated, such embryos (DVE-ablated embryos) showed deregulated expression of Nodal and Wnt3 and ectopically formed the primitive streak at the proximal portion of the embryo. The DVE and anterior visceral endoderm (AVE) are implicated in the development of neurectoderm. We found that the distal epiblast of E5.5 embryo rotates anteriorly by the beginning of gastrulation. These cells remained to be anteriorly located during gastrulation and contributed to the ectoderm in the anterior side of the embryo. This indicates that the distal epiblast of E5.5 embryo becomes neurectoderm in normal development. In DVE-ablated embryos, the distal epiblast did not show any movement during culture and was abnormally fated to early definitive endoderm lineage. The data suggest that down-regulation of Nodal signaling in the distal epiblast of E5.5 embryo may be an initial step of neural development.
Miura
Shigeto
S
Molecular Developmental Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, North Carolina, USA. shi@stowers-institute.org
Mishina
Yuji
Y
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D066298:In Vitro Techniques; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D055457:Nodal Protein; D015398:Signal Transduction; D013270:Stomach / Q000196:embryology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D055457:Nodal Protein; C526008:Nodal protein, mouse; D016212:Transforming Growth Factor beta