The Proneural Gene Ascl1 Controls the Development of Spinal CSF-Contacting Neurons

DI BELLA, D.; CARCAGNO, A.; LANUZA, G.M.

Mexico DF

Simposio; Stem Cells Network Symposium; 2011

Understanding the ontogenetic mechanisms that control the diversification of cell types in the central nervous system is one of the central problems in developmental neurobiology. We have recently identified that the cluster of Cerebrospinal fluid contacting neurons (CCNs) in the central canal of the spinal cord, are a subset of V2 neurons. CCNs are generated late during mouse embryonic development when spinal cord progenitor cells are committed toward glial cell fates. We found that the bHLH-containing proneural protein Ascl1 (Achaete Scute Complex like-1) is expressed in late neuroepithelial cells corresponding to the ventral p2 domain, spatially correlating with the development of CCNs. Short-term lineage tracing experiments indicated that the transcription factor Ascl1 is expressed in CCN progenitors. Additionally, using mouse embryos lacking Ascl1, we found that this transcription factor is required for the correct differentiation of CCNs. Furthermore, the loss of Ascl1 selectively affects CCN development as cell populations generated earlier from the p2 domain remain unaffected. These results show that the proneural transcription factor Ascl1 is expressed in spinal ventral late progenitors that give rise to CCNs and that Ascl1 plays an essential role in their genesis in a cell autonomous manner.