Ascl1 regulates late neurogenic events in the ventral neural tube

DANIELA DI BELLA; ABEL CARCAGNO; LUCIANO BRUM; GUILLERMO LANUZA

Mar del Plata

Congreso; 9. XXX Congreso anual de la Sociedad Argentina de Investigación en Neurociencias 2015; 2015

Sociedad Argentina de Investigación en Neurociencias

Despite the effort invested in the last decades, the regulatory networks that control lineage specification in the developing central nervous system are not completely understood. We have identified a late-born population of spinal neurons that originate from ventral progenitors while the neuroepithelium is committed towards gliogenesis.These neurons were identified as CerebroSpinal Fluid-contacting Neurons (CSF-cN). The aim of this work is to determine the genetic mechanisms involved in the differentiation of CSF-cN. Genetic labeling and expression analysis in the mouse spinal cord show that the bHLHcontaining proneural protein Ascl1 is expressed in CSF-cN lineage from the progenitor state. Using knock-out mice, we show that Ascl1 is specifically required for CSF-cN development and cannot be replaced by other proneural genes. Cell fate tracings together with Ascl1 mosaic deletion show that Ascl1 regulates CSF-cN differentiation in a cell autonomous manner. We genetically labeled prospective CSF-cN progenitors in Ascl1 mutant background. Based on their morphology, marker expression and electrophysiology, we showed that late neuronal progenitors that fail to acquire CSF-cN identity becomeependymal cells that cover the surface of the central canal.Our results show that Ascl1 is expressed in spinal ventral late progenitors that give rise to CSF-cN and is conferring specific neuronal potential to late ventral progenitors in the amniote spinal cord.