A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations.

Journal Article (Journal Article)

Basement membranes (BMs) are ubiquitous extracellular matrices whose composition remains elusive, limiting our understanding of BM regulation and function. By developing a bioinformatic and in vivo discovery pipeline, we define a network of 222 human proteins and their animal orthologs localized to BMs. Network analysis and screening in C. elegans and zebrafish uncovered BM regulators, including ADAMTS, ROBO, and TGFβ. More than 100 BM network genes associate with human phenotypes, and by screening 63,039 genomes from families with rare disorders, we found loss-of-function variants in LAMA5 , MPZL2 , and MATN2 and show that they regulate BM composition and function. This cross-disciplinary study establishes the immense complexity of BMs and their impact on in human health.

Full Text

Duke Authors

Cited Authors

  • Jayadev, R; Morais, MRPT; Ellingford, JM; Srinivasan, S; Naylor, RW; Lawless, C; Li, AS; Ingham, JF; Hastie, E; Chi, Q; Fresquet, M; Koudis, N-M; Thomas, HB; O'Keefe, RT; Williams, E; Adamson, A; Stuart, HM; Banka, S; Smedley, D; Genomics England Research Consortium, ; Sherwood, DR; Lennon, R

Published Date

  • May 2022

Published In

Volume / Issue

  • 8 / 20

Start / End Page

  • eabn2265 -

PubMed ID

  • 35584218

Pubmed Central ID

  • PMC9116610

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

International Standard Serial Number (ISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.abn2265

Language

  • eng