ASCL1 AND NEUROGENIN3 SPECIFY NEURONAL SUBTYPE IDENTITY IN THE VENTRAL NEURAL TUBE

GUILLERMO LANUZA; ABEL CARCAGNO; DANIELA DI BELLA

San Pablo

Congreso; VIII International Meeting of the Latin American society for Development Biology; 2015

LATIN AMERICAN SOCIETY FOR DEVELOPMENTAL BIOLOGY (LASDB)

The development of the nervous system is critically dependent on the production of functionally diverse neuronal cell types at their correct locations. In the embryonic neural tube, dorso-ventral signaling has emerged as a fundamental mechanism for generating neuronal diversity. By contrast, far less is known about how different neuronal cell types are organized along the rostro-caudal axis. In the developing neural tube of amniotes, hindbrain serotonergic neurons and spinal glutamatergic V3 interneurons are produced from ventral p3 progenitors, which possess a common transcriptional identity but are confined to distinct anterior-posterior territories. In this study, we show that the expression of the transcription factor Neurogenin3 (Neurog3) in the spinal cord controls the correct specification of p3-derived neurons. Gain- and loss-of-function manipulations in the chick and mouse embryo show that Neurog3 switches ventral progenitors from a serotonergic to V3 differentiation program by repressing Ascl1 in spinal p3 progenitors through a mechanism dependent on Hesproteins. In this way, Neurog3 serves as a mechanism for interpreting anterior-posterior signaling to establish the posterior boundary of the serotonergic system by actively suppressing serotonergic specification in the spinal cord. These results explain how equivalent p3 progenitors within the hindbrain and the spinal cord produce functionally distinct neuron cell types.