Regulación transcripcional de la diferenciación de las neuronas que contactan el fluido cerebroespinal

ABEL CARCAGNO; DANIELA DI BELLA; GUILLERMO LANUZA

Chascomús

Taller; III Taller de Biología Celular y del Desarrollo 2016; 2016

In the last 20 years, we have reached a huge understanding of the genetic mechanisms that control neuronal specification in the vertebrate neural tube. We have recently identified a late neurogenic event in the spinal cord that takes place simultaneously with glial differentiation, at stages considered non-neurogenic. We have found that the transcription factor Ascl1 is expressed in late ventral progenitors and initiates neuronal differentiation to produce cerebrospinal fluid-contacting neurons (CSF-cN), while the rest of the spinal cord progenitors are committed to glial fates. In this work, we show that the transcription factors Gata3 and Gata2 are sequentially activated during the acquisition of CSF-cN identity. The expression of Gata3/2 is restricted to postmitotic stages, and lays downstream of Ascl1. Gata3 is necessary for appropriate CSF-cN differentiation, as Gata3 conditional knock-out mice have a severe reduction in the number of CSF-cNs. However, a subpopulation of CSF-cN remains unaffected in Gata3-cKO, indicating that, although Gata3 is normally present in this subset, it is dispensable for their differentiation. In looking for potential compensatory actions of Gata2, we generated Gata3;Gata2 double conditional knock-outs and found that in the absence of both Gata transcription factors the complete cohort of CSF-cNs, including those remaining in Gata3-cKO, failed to be specified. In summary, our study identified that the transcription factors Gata3/2 are expressed during CSF-cN differentiation and that Gata3/2 activity is essential to specify the identity of late-born neurons of mouse spinal cord.