PLoS Biology (Apr 2024)

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

  • Suchit Ahuja,
  • Cynthia Adjekukor,
  • Qing Li,
  • Katrinka M Kocha,
  • Nicole Rosin,
  • Elodie Labit,
  • Sarthak Sinha,
  • Ankita Narang,
  • Quan Long,
  • Jeff Biernaskie,
  • Peng Huang,
  • Sarah J Childs

DOI
https://doi.org/10.1371/journal.pbio.3002590
Journal volume & issue
Vol. 22, no. 4
p. e3002590

Abstract

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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.