Expression of the bHLH-Transcription Factor Ascl1 Is Specifically Required for the Development of a subset of V2 Spinal Neurons.

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

Hueta Grande

Congreso; Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2011

Sociedad Argentina de Neurociencias

One central problem in developmental neurobiology is to understand the mechanisms that control neuronal diversification in the nervous system. We identified that cerebrospinal fluid contacting neurons (CSF-cN) in the spinal cord are a subset of V2 neurons that differentiate late during mouse embryonic development. In searching for potential controllers of CSF-cN specification, we found that the proneural protein Ascl1 is expressed in a group of ventral neural tube progenitors, correlating spatially and temporally with CSF-cN development. Expression analysis and short-term lineage tracings indicated that this transcription factor is expressed in CSF-cN progenitors. In addition, we found that in Ascl1-/- mice CSF-cN population is missing, while other cell types generated earlier from the same domain remain unaffected. This phenotype is not rescued by another proneural protein, Neurogenin2, suggesting that Ascl1 activity is specifically required. Finally, taking advantage of the temporally restricted expression of Ascl1 in Foxn4 null mice, we concluded that Ascl1 exerts its actions around the time of CSF-cN differentiation. In summary, our results show that Ascl1 is expressed in spinal ventral late CSF-cN progenitors and that it plays an essential and specific role in their genesis.