Soortspecifieke snelheden van lipidenmetabolisme bepalen de tijdschaal van corticogenese via de dynamiek van eiwitacetylatie

Neurogenesis is a key event of neural development, by which neural stem/progenitor cells (NSPC) stop self-renewing and dividing, to convert to postmitotic neurons. The delicate balance between self-renewal and differentiation of NSPC is controlled by intrinsic and extrinsic cues, in particular transcription factors and morphogen signals (Bonnefont and Vanderhaeghen, 2021; Villalba et al., 2020)). On the other hand, recent evidence have uncovered the key influence of mechanisms once considered to be merely permissive: cell metabolism and mitochondria dynamics (Iwata et al., 2020; Khacho et al., 2016). In particular, recent findings from the host lab indicate that mitochondria control the neurogenic fate transition right after the last cell division; during a critical period that is doubled in human vs mouse species, but the underlying molecular mechanisms remain poorly understood (Iwata et al., 2020). In this project we will determine how mitochondria dynamics and function interplay with developmental cues during neuronal fate transition. In particular we will follow the hypothesis that the mitochondria remodeling that occurs during neurogenesis leads to to the generation of specific metabolites that will then influence post-translational modifications, in particular Histones. This will next lead to chromatin remodeling and subsequent changes in gene expression enabling neurogenesis.