Simposio de expertos: Diversidad neuronal, una cuestión de tiempo y espacio

LANUZA GM

Congreso; Reunión anual de la Sociedad Argentina de Biología; 2021

Sociedad Argentina de Biología, SAB

Establishing neuronal diversity in the developing spinal cord: a matter of time and space. Diversidad neuronal en la médula espinal en desarrollo: una cuestión de tiempo y espacio. Guillermo Lanuza. Fundación Instituto Leloir, IIBBA-CONICET. Ciudad Autónoma de Buenos Aires, Argentina. Generation of neurons at the right time, location, and number is essential for building a functional nervous system. Considerable progress has been made in understanding the mechanisms that control the production of specialized neuronal types. Positional identity has emerged as a fundamental organizing principles governing neuronal subtype diversification. However, how timing of differentiation contributes to cell diversity in the developing spinal cord is still pending. We have identified the generation of neurons during advanced embryonic stages, at the ?gliogenic phase? previously considered non-neurogenic. These late neurogenic events exclusively give rise to CerebroSpinal Fluid-contacting Neurons (CSF cN), an anatomically discrete cell type of the ependymal area of the spinal cord. We identified that the transcription factors Ascl1, Gata3 and Gata2 sequentially control the specification of CSF-cNs. With genetic fate mappings and time-controlled deletions in the mouse, we demonstrate that CSF-cNs derive from progenitors expressing the proneural protein Ascl1, with Ascl1 triggering late neurogenesis in the amniote spinal cord. Ascl1 abrogation transforms prospective CSF-cN progenitors into ependymocytes, demonstrating that late spinal progenitors have the potential to produce neurons and that Ascl1 balances the neuronal and non-neuronal composition of the spinal central canal. Furthermore, downstream of Ascl1, the acquisition of the precise CSF-cN identity depends on the postmitotic action of the transcription factors Gata3 and Gata2. In summary, we demonstrate that Ascl1-Gata3/2 are essential components of the temporally restricted transcriptional program that sustains spinal cord late-born neuron specification.