The development of brain pericytes requires expression of the transcription factor nkx3.1 in intermediate precursors.


Journal

PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755

Informations de publication

Date de publication:
29 Apr 2024
Historique:
received: 21 06 2023
accepted: 14 03 2024
medline: 29 4 2024
pubmed: 29 4 2024
entrez: 29 4 2024
Statut: aheadofprint

Résumé

Brain pericytes are one of the critical cell types that regulate endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. The genetic pathways guiding undifferentiated cells into mature pericytes are not well understood. We show here that pericyte precursor populations from both neural crest and head mesoderm of zebrafish express the transcription factor nkx3.1 develop into brain pericytes. We identify the gene signature of these precursors and show that an nkx3.1-, foxf2a-, and cxcl12b-expressing pericyte precursor population is present around the basilar artery prior to artery formation and pericyte recruitment. The precursors later spread throughout the brain and differentiate to express canonical pericyte markers. Cxcl12b-Cxcr4 signaling is required for pericyte attachment and differentiation. Further, both nkx3.1 and cxcl12b are necessary and sufficient in regulating pericyte number as loss inhibits and gain increases pericyte number. Through genetic experiments, we have defined a precursor population for brain pericytes and identified genes critical for their differentiation.

Identifiants

pubmed: 38683849
doi: 10.1371/journal.pbio.3002590
pii: PBIOLOGY-D-23-01564
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e3002590

Informations de copyright

Copyright: © 2024 Ahuja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

Auteurs

Suchit Ahuja (S)

Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada.
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.

Cynthia Adjekukor (C)

Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada.
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.

Qing Li (Q)

Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada.
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.

Katrinka M Kocha (KM)

Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada.
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.

Nicole Rosin (N)

Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada.

Elodie Labit (E)

Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada.

Sarthak Sinha (S)

Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada.

Ankita Narang (A)

Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.

Quan Long (Q)

Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada.
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.

Jeff Biernaskie (J)

Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.
Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada.

Peng Huang (P)

Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada.
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.

Sarah J Childs (SJ)

Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada.
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.

Classifications MeSH