| First Author | Zupančič M | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 8631 |
| PubMed ID | 39366958 | Mgi Jnum | J:355329 |
| Mgi Id | MGI:7737992 | Doi | 10.1038/s41467-024-52762-z |
| Citation | Zupancic M, et al. (2024) Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons by ONECUT3. Nat Commun 15(1):8631 |
| abstractText | 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 complexity in Onecut3-containing neurons, while genetic deletion of Onecut3/ceh-48 in C. elegans impaired neurocircuit wiring, and sensory discrimination-based behaviors. Thus, ONECUT3, conserved across neuronal subtypes and many species, underpins the polarization and morphological plasticity of phenotypically distinct neurons that descend from a common pool of Ascl1(+) progenitors in the hypothalamus. |
