CONICET | Buscador de Institutos y Recursos Humanos

Neurogenin3 is a key regulator in serotonergic vs. glutamatergic neuronal cell fate, Carcagno A, Di Bella D, Lanuza G. Reunión Anual Sociedad Argentina de Neurociencias (SAN). Cordoba. 2014. The production of functionally diverse neuronal cell types at their correct locations requires the acquisition of specific progenitor identities in response to extrinsic positional cues. In the developing neural tube of amniotes, hindbrain serotonergic (5-HT) neurons and spinal V3 glutamatergic interneurons are produced from ventral progenitors, which possess a common transcriptional identity but are confined to distinct anterior-posterior territories. It is not completely understood how discrete progenitor pools expressing a seemingly identical molecular code give rise to divergent neuronal fates. In this study, we identify that the expression of the transcription factor Neurogenin3 (Neurog3) in the spinal cord controls the correct specification of ventral neural tube cells. Gain-of-function experiments in the chick embryo show that Neurog3 represses the expression of the 5-HT determinant Ascl1 through a mechanism that is dependent on the activity of Hes proteins.Conversely, the spinal cord of Neurog3 mutant mice displays abnormal elevated levels of Ascl1, which triggers the ectopic induction of the serotonergic differentiation program sequentially controlled by the transcription factors Gata2, Lmx1b and Pet1. The ectopic spinal 5-HT neuron production in Neurog3 mutant mice resembles the serotonergic system of aquatic vertebrates, which interestingly lack Neurog3 expression. In summary, our results show that Neurog3 serves as a mechanism for interpreting anterior-posterior signaling to impose the caudal border for the serotonergic rafe system in amniotes, and explain how equivalent progenitors within the hindbrain and the spinal cord can produce distinct functional neuron cell types.