Oxygen Tension and the VHL-Hif1α Pathway Determine Onset of Neuronal Polarization and Cerebellar Germinal Zone Exit.


Journal

Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320

Informations de publication

Date de publication:
20 05 2020
Historique:
received: 12 12 2019
revised: 04 02 2020
accepted: 19 02 2020
pubmed: 19 3 2020
medline: 22 8 2020
entrez: 19 3 2020
Statut: ppublish

Résumé

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 1α (Hif1α) pathway regulate polarization and maturation of post-mitotic cerebellar granule neurons (CGNs). At early postnatal stages with low GZ vascularization, Hif1α restrains CGN-progenitor cell-cycle exit. Unexpectedly, cell-intrinsic VHL-Hif1α 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.

Identifiants

pubmed: 32183943
pii: S0896-6273(20)30148-3
doi: 10.1016/j.neuron.2020.02.025
pmc: PMC7244394
mid: NIHMS1574245
pii:
doi:

Substances chimiques

Hypoxia-Inducible Factor 1, alpha Subunit 0
Von Hippel-Lindau Tumor Suppressor Protein EC 2.3.2.27
Oxygen S88TT14065

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

607-623.e5

Subventions

Organisme : Medical Research Council
ID : MC_PC_17230
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : P01 NS083513
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS104029
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS066936
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

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Auteurs

Jan A Kullmann (JA)

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Molecular Neurobiology Group, Institute of Physiological Chemistry, Philipps University of Marburg, 35032 Marburg, Germany.

Niraj Trivedi (N)

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Danielle Howell (D)

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Christophe Laumonnerie (C)

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Vien Nguyen (V)

Department of Pediatrics and Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.

Shalini S Banerjee (SS)

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Daniel R Stabley (DR)

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Abbas Shirinifard (A)

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

David H Rowitch (DH)

Department of Pediatrics and Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pediatrics and Wellcome Trust-MRC Stem Cell Institute, University of Cambridge, Hills Road, Cambridge CB2 0AN, UK.

David J Solecki (DJ)

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: david.solecki@stjude.org.

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Classifications MeSH