1. Perivascular neurons instruct 3D vascular lattice formation via neurovascular contact.
- Author
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Toma K, Zhao M, Zhang S, Wang F, Graham HK, Zou J, Modgil S, Shang WH, Tsai NY, Cai Z, Liu L, Hong G, Kriegstein AR, Hu Y, Körbelin J, Zhang R, Liao YJ, Kim TN, Ye X, and Duan X
- Subjects
- Animals, Female, Male, Mice, Ion Channels metabolism, Mice, Inbred C57BL, Retinal Ganglion Cells metabolism, Retinal Vessels metabolism, Cerebellum metabolism, Cerebellum blood supply, Cerebellum cytology, Neurons metabolism, Retina cytology, Retina metabolism
- Abstract
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., Competing Interests: Declaration of interests J.Z. and X.Y. are employees of Genentech/Roche. J.K. is listed as an inventor on Boehringer Ingelheim’s patent (AAV-BR1, #10696717)., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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