| First Author | Kullmann JA | Year | 2020 |
| Journal | Neuron | Volume | 106 |
| Issue | 4 | Pages | 607-623.e5 |
| PubMed ID | 32183943 | Mgi Jnum | J:298376 |
| Mgi Id | MGI:6449493 | Doi | 10.1016/j.neuron.2020.02.025 |
| Citation | Kullmann JA, et al. (2020) Oxygen Tension and the VHL-Hif1alpha Pathway Determine Onset of Neuronal Polarization and Cerebellar Germinal Zone Exit. Neuron 106(4):607-623.e5 |
| abstractText | Postnatal brain circuit assembly is driven by temporally regulated intrinsic and cell-extrinsic cues that organize neurogenesis, migration, and axo-dendritic specification in post-mitotic neurons. While cell polarity is an intrinsic organizer of morphogenic events, environmental cues in the germinal zone (GZ) instructing neuron polarization and their coupling during postnatal development are unclear. We report that oxygen tension, which rises at birth, and the von Hippel-Lindau (VHL)-hypoxia-inducible factor 1alpha (Hif1alpha) pathway regulate polarization and maturation of post-mitotic cerebellar granule neurons (CGNs). At early postnatal stages with low GZ vascularization, Hif1alpha restrains CGN-progenitor cell-cycle exit. Unexpectedly, cell-intrinsic VHL-Hif1alpha pathway activation also delays the timing of CGN differentiation, germinal zone exit, and migration initiation through transcriptional repression of the partitioning-defective (Pard) complex. As vascularization proceeds, these inhibitory mechanisms are downregulated, implicating increasing oxygen tension as a critical switch for neuronal polarization and cerebellar GZ exit. |
