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Publication : Combinatorial signalling controls Neurogenin2 expression at the onset of spinal neurogenesis.

First Author  Ribes V Year  2008
Journal  Dev Biol Volume  321
Issue  2 Pages  470-81
PubMed ID  18590718 Mgi Jnum  J:139732
Mgi Id  MGI:3809995 Doi  10.1016/j.ydbio.2008.06.003
Citation  Ribes V, et al. (2008) Combinatorial signalling controls Neurogenin2 expression at the onset of spinal neurogenesis. Dev Biol 321(2):470-81
abstractText  A central issue during embryonic development is to define how different signals cooperate in generating unique cell types. To address this issue, we focused on the function and the regulation of the proneural gene Neurogenin2 (Neurog2) during early mouse spinal neurogenesis. We showed that Neurog2 is first expressed in cells within the neural plate anterior to the node from the 5 somite-stage. The analysis of Neurog2 mutants established a role for this gene in triggering neural differentiation during spinal cord elongation. We identified a 798 base pair enhancer element (Neurog2-798) upstream of the Neurog2 coding sequence that directs the early caudal expression of Neurog2. Embryo culture experiments showed that Retinoic Acid (RA), Sonic hedgehog (Shh) and Fibroblast Growth Factor signals act in concert on this enhancer to control the spatial and temporal induction of Neurog2. We further demonstrated by transgenesis that two RA response elements and a Gli binding site within the Neurog2-798 element are absolutely required for its activity, strongly suggesting that the regulation of Neurog2 early expression by RA and Shh signals is direct. Our data thus support a model where signal integration at the level of a single enhancer constitutes a key mechanism to control the onset of neurogenesis.
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