PUBLICATION
The development of brain pericytes requires expression of the transcription factor nkx3.1 in intermediate precursors
- Authors
- Ahuja, S., Adjekukor, C., Li, Q., Kocha, K.M., Rosin, N., Labit, E., Sinha, S., Narang, A., Long, Q., Biernaskie, J., Huang, P., Childs, S.J.
- ID
- ZDB-PUB-240430-3
- Date
- 2024
- Source
- PLoS Biology 22: e3002590e3002590 (Journal)
- Registered Authors
- Childs, Sarah J., Huang, Peng, Kocha, Katrinka
- Keywords
- none
- Datasets
- GEO:GSE232763, GEO:GSE232762, GEO:GSE232163
- MeSH Terms
-
- Animals
- Brain*/embryology
- Brain*/metabolism
- Cell Differentiation*/genetics
- Chemokine CXCL12/genetics
- Chemokine CXCL12/metabolism
- Gene Expression Regulation, Developmental
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism
- Mesoderm/cytology
- Mesoderm/metabolism
- Neural Crest/cytology
- Neural Crest/metabolism
- Pericytes*/cytology
- Pericytes*/metabolism
- Receptors, CXCR4/genetics
- Receptors, CXCR4/metabolism
- Signal Transduction
- Transcription Factors*/genetics
- Transcription Factors*/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 38683849 Full text @ PLoS Biol.
Citation
Ahuja, S., Adjekukor, C., Li, Q., Kocha, K.M., Rosin, N., Labit, E., Sinha, S., Narang, A., Long, Q., Biernaskie, J., Huang, P., Childs, S.J. (2024) The development of brain pericytes requires expression of the transcription factor nkx3.1 in intermediate precursors. PLoS Biology. 22:e3002590e3002590.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping