Dataset Information

Mural Wnt/β-catenin signaling regulates Lama2 expression to promote neurovascular unit maturation.

ABSTRACT: Neurovascular unit and barrier maturation rely on vascular basement membrane (vBM) composition. Laminins, a major vBM component, are crucial for these processes, yet the signaling pathway(s) that regulate their expression remain unknown. Here, we show that mural cells have active Wnt/β-catenin signaling during central nervous system development in mice. Bulk RNA sequencing and validation using postnatal day 10 and 14 wild-type versus adenomatosis polyposis coli downregulated 1 (Apcdd1-/-) mouse retinas revealed that Lama2 mRNA and protein levels are increased in mutant vasculature with higher Wnt/β-catenin signaling. Mural cells are the main source of Lama2, and Wnt/β-catenin activation induces Lama2 expression in mural cells in vitro. Markers of mature astrocytes, including aquaporin 4 (a water channel in astrocyte endfeet) and integrin-α6 (a laminin receptor), are upregulated in Apcdd1-/- retinas with higher Lama2 vBM deposition. Thus, the Wnt/β-catenin pathway regulates Lama2 expression in mural cells to promote neurovascular unit and barrier maturation.

SUBMITTER: Biswas S

PROVIDER: S-EPMC9578690 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Mural Wnt/β-catenin signaling regulates Lama2 expression to promote neurovascular unit maturation.

Biswas Saptarshi S Shahriar Sanjid S Giangreco Nicholas P NP Arvanitis Panos P Winkler Markus M Tatonetti Nicholas P NP Brunken William J WJ Cutforth Tyler T Agalliu Dritan D

Development (Cambridge, England) 20220913 17

Neurovascular unit and barrier maturation rely on vascular basement membrane (vBM) composition. Laminins, a major vBM component, are crucial for these processes, yet the signaling pathway(s) that regulate their expression remain unknown. Here, we show that mural cells have active Wnt/β-catenin signaling during central nervous system development in mice. Bulk RNA sequencing and validation using postnatal day 10 and 14 wild-type versus adenomatosis polyposis coli downregulated 1 (Apcdd1-/-) mouse ...[more]

PMID: 36098369

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Dataset Information

Mural Wnt/β-catenin signaling regulates Lama2 expression to promote neurovascular unit maturation.

Publications

Mural Wnt/β-catenin signaling regulates Lama2 expression to promote neurovascular unit maturation.

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