Skull progenitor cell-driven meningeal lymphatic restoration improves neurocognitive functions in craniosynostosis.

ABSTRACT: The meninges lie in the interface between the skull and brain, harboring lymphatic vasculature and skull progenitor cells (SPCs). How the skull and brain communicate remains largely unknown. We found that impaired meningeal lymphatics and brain perfusion drive neurocognitive defects in Twist1^+/- mice, an animal model of craniosynostosis recapitulating human Saethre-Chotzen syndrome. Loss of SPCs leads to skull deformities and elevated intracranial pressure (ICP), whereas transplanting SPCs back into mutant mice mitigates lymphatic and brain defects through two mechanisms: (1) decreasing elevated ICP by skull correction and (2) promoting the growth and migration of lymphatic endothelial cells (LECs) via SPC-secreted vascular endothelial growth factor-C (VEGF-C). Treating Twist1

SUBMITTER: Ma L 

PROVIDER: S-EPMC10842404 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature