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Retinoic acid receptors exhibit cell-autonomous functions in cranial neural crest cells.

Abstract : Previous work has emphasized the crucial role of retinoic acid (RA) in the ontogenesis of the vast majority of mesenchymal structures derived from the neural crest cells (NCC), which migrate through, or populate, the frontonasal process and branchial arches. Using somatic mutagenesis in the mouse, we have selectively ablated two or three retinoic acid receptors (i.e., RARalpha/RARbeta, RARalpha/RARgamma and RARalpha/RARbeta/RARgamma) in NCC. By rigorously analyzing these mutant mice, we found that survival and migration of NCC is normal until gestational day 10.5, suggesting that RAR-dependent signaling is not intrinsically required for the early steps of NCC development. However, ablation of Rara and Rarg genes in NCC yields an agenesis of the median portion of the face, demonstrating that RARalpha and RARgamma act cell-autonomously in postmigratory NCC to control the development of structures derived from the frontonasal process. In contrast, ablation of the three Rar genes in NCC leads to less severe defects of the branchial arches derived structures compared with Rar compound null mutants. Therefore, RARs exert a function in the NCC as well as in a separated cell population. This work demonstrates that RARs use distinct mechanisms to pattern cranial NCC.
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Submitted on : Thursday, September 23, 2010 - 9:55:37 AM
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Valérie Dupé, Isabelle Pellerin. Retinoic acid receptors exhibit cell-autonomous functions in cranial neural crest cells.. Developmental Dynamics, Wiley, 2009, 238 (10), pp.2701-11. ⟨10.1002/dvdy.22087⟩. ⟨inserm-00413491⟩



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