Ligand-specific endothelial Notch signaling coordinates brain pericyte specification and expansion
- 1Affiliated Hospital of Guangdong Medical University
Abstract
Pericyte specification and expansion must be coordinated with vascular growth to establish a functional cerebrovascular network, yet how endothelial signals control these distinct developmental transitions remains incompletely understood. Here, using genetic manipulation, single-cell transcriptomic analysis, and longitudinal in vivo imaging in zebrafish, we identify ligand-specific endothelial Notch signaling as a mechanism coordinating brain pericyte development. Endothelial Jag2b is required for efficient pericyte specification from pericerebral progenitor pools and subsequently promotes Notch-dependent pericyte proliferation and population expansion. By contrast, endothelial Dll4 restrains pericyte proliferation and functionally opposes Jag2b-dependent expansion, demonstrating that distinct endothelial Notch ligands generate different developmental outputs. Endothelial Notch activation increases jag2b expression, and genetic interaction analyses establish Jag2b as an important mediator of Notch-dependent pericyte expansion. Moreover, genetic disruption of piezo1 reduces brain pericyte abundance, whereas endothelial jag2b expression rescues this phenotype, placing Jag2b downstream of Piezo1-dependent hemodynamic signaling. Together, these findings reveal a ligand-specific endothelial Notch program that integrates hemodynamic cues with endothelial-pericyte communication to coordinate the specification and expansion of brain pericytes during cerebrovascular development.
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BibTeX
@misc{zhang2026ligandspecific,
title = {{Ligand-specific endothelial Notch signaling coordinates brain pericyte specification and expansion}},
author = {J. Zhang and H. Zi and C. Dang and W. Sima and X. Li and G. Ning and L. Sun and Q. Wang},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.756680},
url = {https://www.biorxiv.org/content/10.64898/2026.10.05.756680v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Ligand-specific endothelial Notch signaling coordinates brain pericyte specification and expansion
AU - J. Zhang
AU - H. Zi
AU - C. Dang
AU - W. Sima
AU - X. Li
AU - G. Ning
AU - L. Sun
AU - Q. Wang
PY - 2026
DA - 2026/10/05
PB - bioRxiv
DO - 10.64898/2026.10.05.756680
UR - https://www.biorxiv.org/content/10.64898/2026.10.05.756680v1
AB - Pericyte specification and expansion must be coordinated with vascular growth to establish a functional cerebrovascular network, yet how endothelial signals control these distinct developmental transitions remains incompletely understood. Here, using genetic manipulation, single-cell transcriptomic analysis, and longitudinal in vivo imaging in zebrafish, we identify ligand-specific endothelial Notch signaling as a mechanism coordinating brain pericyte development. Endothelial Jag2b is required for efficient pericyte specification from pericerebral progenitor pools and subsequently promotes Notch-dependent pericyte proliferation and population expansion. By contrast, endothelial Dll4 restrains pericyte proliferation and functionally opposes Jag2b-dependent expansion, demonstrating that distinct endothelial Notch ligands generate different developmental outputs. Endothelial Notch activation increases jag2b expression, and genetic interaction analyses establish Jag2b as an important mediator of Notch-dependent pericyte expansion. Moreover, genetic disruption of piezo1 reduces brain pericyte abundance, whereas endothelial jag2b expression rescues this phenotype, placing Jag2b downstream of Piezo1-dependent hemodynamic signaling. Together, these findings reveal a ligand-specific endothelial Notch program that integrates hemodynamic cues with endothelial-pericyte communication to coordinate the specification and expansion of brain pericytes during cerebrovascular development.
ER -