Gene regulatory network controlling late neurogenesis in the developing spinal cord

DANIELA DI BELLA; ABEL CARCAGNO; CRISTINA MONZON; GUILLERMO LANUZA

Huerta grande

Congreso; 11. XXIX Congreso anual de la Sociedad Argentina de Investigación en Neurociencias; 2014

Sociedad Argentina de Investigación en Neurociencias

The regulatory networks that control lineage specification in the developing nervous system are not completely understood. We identified the critical role of two transcriptional regulators controling late neurogenesis in the embryonic neural tube. At developmental stages in which spinal cord precursor cells are massively committed towards gliogenesis, we found that the ventral neuroepithelium gives also rise to a defined class of neurons: Cerebrospinal Fluid-contacting Neurons (CSF-cN). Genetic labeling and expression analysis in the mouse spinal cord show that the transcription factors Ascl1, Gata3 and Gata2, are sequentially expressed in CSF-cN lineage. Using knock-out mice, we show that Ascl1 is necessary for CSF-cN development. By performing time restricted deletions of Ascl1, we found that Ascl1 initiates CSF-cN differentiation and it is also necessary at postmitotic stages of newborn neurons. Gata3 lays genetically downstream of Ascl1, as Gata3 is not expressed in ventral progenitors in Ascl1 mutant. The analysis of Gata3 knockout mice and conditional deletion indicate that Gata3 instructs postmitotic CSF-cN differentiation. Fate-mapping experiments show that in the absence of Ascl1, late neuronal progenitors that fail to acquire CSF-cN identity become into ependymal cells that cover the surface of the central canal. In summary, we demonstrate that both Ascl1 and Gata3 are sequentially induced and both control late neuronal differentiation in the developing spinal cord.