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Cited by 378

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Retinoic acid synthesis and hindbrain patterning in the mouse embryo

Niederreither, Karen, Vermot, Julien, Schuhbaur, Brigitte, Chambon, Pierre, Dollé, Pascal·2000·Development
DOI 10.1242/dev.127.1.75
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Abstract

Targeted disruption of the murine retinaldehyde dehydrogenase 2 (Raldh2) gene precludes embryonic retinoic acid (RA) synthesis, leading to midgestational lethality (Niederreither, K., Subbarayan, V., Dollé, P. and Chambon, P. (1999). Nature Genet. 21, 444-448). We describe here the effects of this RA deficiency on the development of the hindbrain and associated neural crest. Morphological segmentation is impaired throughout the hindbrain of Raldh2−/− embryos, but its caudal portion becomes preferentially reduced in size during development. Specification of the midbrain region and of the rostralmost rhombomeres is apparently normal in the absence of RA synthesis. In contrast, marked alterations are seen throughout the caudal hindbrain of mutant embryos. Instead of being expressed in two alternate rhombomeres (r3 and r5), Krox20 is expressed in a single broad domain, correlating with an abnormal expansion of the r2-r3 marker Meis2. Instead of forming a defined r4, Hoxb1- and Wnt8A-expressing cells are scattered throughout the caudal hindbrain, whereas r5/r8 markers such as kreisler or group 3/4 Hox genes are undetectable or markedly downregulated. Lack of alternate Eph receptor gene expression could explain the failure to establish rhombomere boundaries. Increased apoptosis and altered migratory pathways of the posterior rhombencephalic neural crest cells are associated with impaired branchial arch morphogenesis in mutant embryos. We conclude that RA produced by the embryo is required to generate posterior cell fates in the developing mouse hindbrain, its absence leading to an abnormal r3 (and, to a lesser extent, r4) identity of the caudal hindbrain cells.

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Metadata

Authors
Niederreither, K., Vermot, J., Schuhbaur, B., Chambon, P., & Dollé, P.
Venue
Development
Publisher
The Company of Biologists
Published
2000-01-01
Volume
127
Issue
1
Pages
75-85
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.127.1.75
OpenAlex
W2129589628
Cited by
378
References
0
FWCI
10.93
Type
journal article
Language
en
Open access
closed

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