The bHLH transcription factor ASCL1 cell-automously controls the differentiation of spinal CSF-contacting neurons

DANIELA DIBELLA*; ABEL CARCAGNO*; GUILLERMO LANUZA

Santa Cruz, Chile

Congreso; V International Meeting of the Latin American society for Development Biology; 2010

Understanding the ontogenetic mechanisms that control the diversification of cell types in thecentral nervous system is one of the central problems in developmental neurobiology. We haverecently identified that the cluster of Cerebrospinal fluid contacting neurons (CCNs) in thecentral canal of the spinal cord, are a subset of V2 neurons. CCNs are generated relatively lateduring mouse embryonic development when spinal cord progenitor cells are committed towardglial cell fates. CCNs have unique morphological and molecular features that allow theirunambiguous identification, including a cellular process through the epithelial barrier of theependyma.We found that the bHLH-containing proneural protein Ascl1 (Achaete Scute Complex like-1) isexpressed in late neuroepithelial cells corresponding to the ventral p2 domain, and that thisexpression spatially correlates with the development of CCNs. Short-term lineage tracingexperiments using the transgenic mouse line Ascl1GFP indicated that the transcription factorAscl1 is expressed in CCN progenitors. In order to assess whether Ascl1 is required for thegeneration of this neural population, we analyzed the differentiation of CCNs in the embryonicspinal cord of mice lacking this transcription factor. By using a combination of CCN markers(PKD2L1, Gata2, Gata3) we found that CCNs fail to develop in Ascl1 mutants. Furthermore, theloss of Ascl1 selectively affects CCN development as cell populations generated earlier from thep2 domain remain unaffected. These results show that the proneural transcription factor Ascl1 isexpressed in spinal ventral late progenitors that give rise to CCNs and that Ascl1 plays anessential role in their genesis in a cell autonomous manner.