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Laminin‐dystroglycan signaling regulates retinal arteriogenesis
Author(s) -
Biswas Saptarshi,
Watters Jared,
Bachay Galina,
Varshney Shweta,
Hunter Dale D.,
Hu Huaiyu,
Brunken William J.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201800232r
Subject(s) - arteriogenesis , dystroglycan , laminin , microbiology and biotechnology , retinal , morphogenesis , biology , noggin , anatomy , chemistry , angiogenesis , cancer research , extracellular matrix , biochemistry , gene , bone morphogenetic protein
ABSTRACT Proper arteriovenous morphogenesis is crucial for maintaining normal tissue perfusion. However, our understanding of how arterial morphogenesis is regulated in the CNS is incomplete. In this study, we asked whether vascular basement membrane (BM) laminins, specifically the γ‐containing isoforms, regulate retinal arterial morphogenesis. We provide evidence that laminin‐γ3 is deposited at both arterial and venous BMs during arte riogenesis. Vascular BM laminin‐γ3 bound dystroglycan (DG), a laminin receptor preferentially expressed by arterial endothelial cells (ECs) during arteriogenesis. Blockade of laminin‐DG binding in vitro led to decreased Delta‐like ligand (DLL)‐4 expression in ECs. Moreover, genetic deletion of the laminin‐γ3‐ and EC‐specific deletion of DG led to similar defects in retinal arteriogenesis, including reduced Dll4 expression, hyperbranching and reduced smooth muscle coverage. These results implicate a newly identified laminin‐g3‐DG signaling cascade that regulates arterial Dll4/Notch signaling to specify and stabilize retinal arteries.—Biswas, S., Watters, J., Bachay, G., Varshney, S., Hunter, D. D., Hu, H., Brunken, W. J. Laminin‐dystroglycan signaling regulates retinal arteriogenesis. 32, 6261–6273 (2018). www.fasebj.org