First Author | Toma K | Year | 2024 |
Journal | Cell | Volume | 187 |
Issue | 11 | Pages | 2767-2784.e23 |
PubMed ID | 38733989 | Mgi Jnum | J:348776 |
Mgi Id | MGI:7643066 | Doi | 10.1016/j.cell.2024.04.010 |
Citation | Toma K, et al. (2024) Perivascular neurons instruct 3D vascular lattice formation via neurovascular contact. Cell 187(11):2767-2784.e23 |
abstractText | The vasculature of the central nervous system is a 3D lattice composed of laminar vascular beds interconnected by penetrating vessels. The mechanisms controlling 3D lattice network formation remain largely unknown. Combining viral labeling, genetic marking, and single-cell profiling in the mouse retina, we discovered a perivascular neuronal subset, annotated as Fam19a4/Nts-positive retinal ganglion cells (Fam19a4/Nts-RGCs), directly contacting the vasculature with perisomatic endfeet. Developmental ablation of Fam19a4/Nts-RGCs led to disoriented growth of penetrating vessels near the ganglion cell layer (GCL), leading to a disorganized 3D vascular lattice. We identified enriched PIEZO2 expression in Fam19a4/Nts-RGCs. Piezo2 loss from all retinal neurons or Fam19a4/Nts-RGCs abolished the direct neurovascular contacts and phenocopied the Fam19a4/Nts-RGC ablation deficits. The defective vascular structure led to reduced capillary perfusion and sensitized the retina to ischemic insults. Furthermore, we uncovered a Piezo2-dependent perivascular granule cell subset for cerebellar vascular patterning, indicating neuronal Piezo2-dependent 3D vascular patterning in the brain. |