Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons by ONECUT3.

ABSTRACT: Acquisition of specialized cellular features is controlled by the ordered expression of transcription factors (TFs) along differentiation trajectories. Here, we find a member of the Onecut TF family, ONECUT3, expressed in postmitotic neurons that leave their Ascl1⁺/Onecut1/2⁺ proliferative domain in the vertebrate hypothalamus to instruct neuronal differentiation. We combined single-cell RNA-seq and gain-of-function experiments for gene network reconstruction to show that ONECUT3 affects the polarization and morphogenesis of both hypothalamic GABA-derived dopamine and thyrotropin-releasing hormone (TRH)⁺ glutamate neurons through neuron navigator-2 (NAV2). In vivo, siRNA-mediated knockdown of ONECUT3 in neonatal mice reduced NAV2 mRNA, as well as neurite co

SUBMITTER: Zupancic M 

PROVIDER: S-EPMC11452682 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature