Identification of Transcription Factors Involved in Differentiation of Late-Born Ventral Spinal Neurons

DI BELLA, D; CARCAGNO, A; PETRACCA, Y.; SARTORETTI, M; LANUZA, G.M.

Montreal

Congreso; 71st Meeting of the Society of Developmental Biology; 2012

Society of Developmental Biology

The regulatory networks that control lineage specification in the developing central nervous system are not completely understood. We have recently identified a novel population of neurons that originate in the ventral neural tube at stages when spinal cord progenitors are committed to glial fates. They are a late-born subset of V2 cells and were identified as CerebroSpinal Fluid-contacting Neurons (CSF-cN). The aim of this work is to determine the mechanisms involved in the differentiation of CSF-cN. Genetic lineage tracing in vivo experiments and expression analysis in mice indicate that CSF-cN progenitors express both the proneural transcription factor Ascl1 and the zinc finger containing transcription factor Gata3. We have found that CSF-cN are missing in Ascl1 mutant mice, while other neuronal cell types generated earlier from the same domain remain unaffected. In order to assess when Ascl1 is needed, we took advantage of the temporally restricted expression of Ascl1 conditional mice, revealing that Ascl1 exerts its critical actions around the time of CSF-cN differentiation. Moreover, our results indicate that Gata3 also plays a key role in CSF-cN development, as this population is severely affected in conditional CNS Gata3 knockouts. We determined that Ascl1 precedes Gata3 expression and that Gata3 is absent in ventral progenitors from Ascl1 mutants. On the contrary, we did not find a change in Ascl1 expression in Gata3 cKOs. In summary, we identified two key and specific regulators of CSF-cN specification. Our results show that Ascl1 and Gata3 act sequentially in controlling late neurogenic events in the ventral neural tube.