Developmental emergence of quiescent-like neural progenitor cells in the zebrafish embryonic brain

Abstract

The mature brain is made up of differentiated neurons and glial cells that are produced by embryonic neural stem and progenitor cells (collectively called neural stem cells (NSCs)) during brain development. In contrast, adult NSCs generate only a limited number of neuronal and glial cell types. Moreover, in contrast to embryonic NSCs, adult NSCs spend most of their time in a non-dividing resting phase called quiescence. In the adult brain, the quiescent NSCs are activated at a low frequency to divide and produce new cells to replace lost or damaged mature cells. Previous studies have demonstrated that about halfway through mammalian brain development, a subset of the embryonic NSCs population slows down their division rate and slowly transition into adult quiescent NSCs (qNSCs). However, the molecular mechanisms that underlie the emergence of the pre-adult SCs remain largely unknown. Here, we explored single-cell transcriptomes from several embryonic stages of zebrafish development in order to determine at what developmental stage transcriptional signatures typical of adult quiescent NSCs first emerge. We identified a subpopulation of embryonic NSCs with a distinct transcriptional profile from other embryonic NSCs. This population shares transcriptional similarities with adult qNSCs including genes known to maintain quiescence. We propose that this population constitute slower cycling embryonic NSCs that may transition into the adult qNSCs of the adult zebrafish brain.