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

Development (Cambridge, England) | 2022

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.

Pubmed ID: 36098369 RIS Download

Associated grants

  • Agency: NEI NIH HHS, United States
    Id: R01 EY033994
  • Agency: NCRR NIH HHS, United States
    Id: S10 RR027699
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH112849
  • Agency: NINDS NIH HHS, United States
    Id: R21 NS118891
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS107344
  • Agency: NHLBI NIH HHS, United States
    Id: R61 HL159949
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM131905

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This is a list of tools and resources that we have found mentioned in this publication.


Anti-Laminin antibody produced in rabbit (antibody)

RRID:AB_477163

This polyclonal targets Laminin antibody produced in rabbit

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Anti-Glial Fibrillary Acidic Protein (GFAP) (antibody)

RRID:AB_2109645

This polyclonal targets Glial Fibrillary Acidic Protein (GFAP)

View all literature mentions

LEF1 (C12A5) Rabbit mAb (antibody)

RRID:AB_823558

This monoclonal targets LEF1 (C12A5) Rabbit mAb

View all literature mentions

Anti-CD31 antibody (antibody)

RRID:AB_726362

This polyclonal targets CD31

View all literature mentions

Caveolin 1 antibody - Caveolae Marker (antibody)

RRID:AB_444314

This polyclonal targets Caveolin 1 antibody - Caveolae Marker

View all literature mentions

Laminin 2 alpha antibody [4H8-2] (antibody)

RRID:AB_298180

This monoclonal targets Laminin 2 alpha antibody [4H8-2]

View all literature mentions

Anti-NG2 Chondroitin Sulfate Proteoglycan (antibody)

RRID:AB_11213678

This polyclonal targets NG2 Chondroitin Sulfate Proteoglycan

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CD 31 Platelet Endothelial Cell Adhesion Molecule (PECAM) (antibody)

RRID:AB_394816

This monoclonal targets 129/Sv mouse-derived endothelioma cell line tEnd.1

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B6.129S1(Cg)-Lama2tm1Eeng/J (organism)

RRID:IMSR_JAX:013786

Mus musculus with name B6.129S1(Cg)-Lama2tm1Eeng/J from IMSR.

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