| First Author | Wendling O | Year | 2001 |
| Journal | Development | Volume | 128 |
| Issue | 11 | Pages | 2031-8 |
| PubMed ID | 11493525 | Mgi Jnum | J:69856 |
| Mgi Id | MGI:2135657 | Doi | 10.1242/dev.128.11.2031 |
| Citation | Wendling O, et al. (2001) Roles of retinoic acid receptors in early embryonic morphogenesis and hindbrain patterning. Development 128(11):2031-8 |
| abstractText | Mutants mice carrying targeted inactivations of both retinoic acid receptor (RAR) alpha and RARgamma (Aalpha/Agamma mutants) were analyzed at different embryonic stages, in order to establish the timing of appearance of defects that we previously observed during the fetal period. We show that embryonic day (E)9.5 Aalpha/Agamma embryos display severe malformations, similar to those already described in retinaldehyde dehydrogenase 2 null mutants. These malformations reflect early roles of retinoic acid signaling in axial rotation, segmentation and closure of the hindbrain; formation of otocysts, pharyngeal arches and forelimb buds; and in the closure of the primitive gut. The hindbrain of E8.5 Aalpha/Agamma embryos shows a posterior expansion of rhombomere 3 and 4 (R3 and R4) markers, but fails to express kreisler, a normal marker of R5 and R6. This abnormal hindbrain phenotype is strikingly different from that of embryos lacking RARalpha and RARbeta (Aalpha/Abetamutants), in which we have previously shown that the territory corresponding to R5 and R6 is markedly enlarged. Administration of a pan-RAR antagonist at E8.0 to wild-type embryos cultured in vitro results in an Aalpha/Abeta-like hindbrain phenotype, whereas an earlier treatment at E7.0 yields an Aalpha/Agamma-like phenotype. Altogether, our data suggest that RARalpha and/or RARgamma transduce the RA signal that is required first to specify the prospective R5/R6 territory, whereas RARbeta is subsequently involved in setting up the caudal boundary of this territory. |
