Alk1 acts in non-endothelial VE-cadherin+ perineurial cells to maintain nerve branching during hair homeostasis

Gopal Chovatiya, Kefei Nina Li, Jonathan Li, Sangeeta Ghuwalewala and Tudorita Tumbar ()
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Gopal Chovatiya: Cornell University
Kefei Nina Li: Cornell University
Jonathan Li: Cornell University
Sangeeta Ghuwalewala: Cornell University
Tudorita Tumbar: Cornell University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Vascular endothelial (VE)-cadherin is a well-recognized endothelial cell marker. One of its interacting partners, the TGF-β receptor Alk1, is essential in endothelial cells for adult skin vasculature remodeling during hair homeostasis. Using single-cell transcriptomics, lineage tracing and gene targeting in mice, we characterize the cellular and molecular dynamics of skin VE-cadherin+ cells during hair homeostasis. We describe dynamic changes of VE-cadherin+ endothelial cells specific to blood and lymphatic vessels and uncover an atypical VE-cadherin+ cell population. The latter is not a predicted adult endovascular progenitor, but rather a non-endothelial mesenchymal perineurial cell type, which forms nerve encapsulating tubular structures that undergo remodeling during hair homeostasis. Alk1 acts in the VE-cadherin+ perineurial cells to maintain proper homeostatic nerve branching by enforcing basement membrane and extracellular matrix molecular signatures. Our work implicates the VE-cadherin/Alk1 duo, classically known as endothelial-vascular specific, in perineurial-nerve homeostasis. This has broad implications in vascular and nerve disease.

Date: 2023
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DOI: 10.1038/s41467-023-40761-5

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