LRIG1-Mediated Inhibition of EGF Receptor Signaling Regulates Neural Precursor Cell Proliferation in the Neocortex.


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
13 10 2020
Historique:
received: 14 05 2020
revised: 17 08 2020
accepted: 21 09 2020
entrez: 14 10 2020
pubmed: 15 10 2020
medline: 22 9 2021
Statut: ppublish

Résumé

Here, we ask how neural stem cells (NSCs) transition in the developing neocortex from a rapidly to a slowly proliferating state, a process required to maintain lifelong stem cell pools. We identify LRIG1, known to regulate receptor tyrosine kinase signaling in other cell types, as a negative regulator of cortical NSC proliferation. LRIG1 is expressed in murine cortical NSCs as they start to proliferate more slowly during embryogenesis and then peaks postnatally when they transition to give rise to a portion of adult NSCs. Constitutive or acute loss of Lrig1 in NSCs over this developmental time frame causes stem cell expansion due to increased proliferation. LRIG1 controls NSC proliferation by associating with and negatively regulating the epidermal growth factor receptor (EGFR). These data support a model in which LRIG1 dampens the stem cell response to EGFR ligands within the cortical environment to slow their proliferation as they transition to postnatal adult NSCs.

Identifiants

pubmed: 33053360
pii: S2211-1247(20)31246-8
doi: 10.1016/j.celrep.2020.108257
pii:
doi:

Substances chimiques

Lrig1 protein, mouse 0
Membrane Glycoproteins 0
Nerve Tissue Proteins 0
ErbB Receptors EC 2.7.10.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108257

Subventions

Organisme : CIHR
Pays : Canada

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

Auteurs

Danielle Jeong (D)

Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Program in Neurosciences and Mental Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada.

Daniela Lozano Casasbuenas (D)

Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.

Archana Gengatharan (A)

CERVO Brain Research Center, Quebec City, QC G1J 2G3, Canada; Department of Psychiatry and Neuroscience, Université Laval, Quebec City, QC G1V 0A6, Canada.

Kyshona Edwards (K)

Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.

Armen Saghatelyan (A)

CERVO Brain Research Center, Quebec City, QC G1J 2G3, Canada; Department of Psychiatry and Neuroscience, Université Laval, Quebec City, QC G1V 0A6, Canada.

David R Kaplan (DR)

Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Program in Neurosciences and Mental Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.

Freda D Miller (FD)

Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Program in Neurosciences and Mental Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.

Scott A Yuzwa (SA)

Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada. Electronic address: scott.yuzwa@utoronto.ca.

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