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

Publication ,  Journal Article
Jayadev, R; Morais, MRPT; Ellingford, JM; Srinivasan, S; Naylor, RW; Lawless, C; Li, AS; Ingham, JF; Hastie, E; Chi, Q; Fresquet, M; Banka, S ...
Published in: Science advances
May 2022

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.

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Published In

Science advances

DOI

EISSN

2375-2548

ISSN

2375-2548

Publication Date

May 2022

Volume

8

Issue

20

Start / End Page

eabn2265

Related Subject Headings

  • Zebrafish
  • Humans
  • Extracellular Matrix Proteins
  • Extracellular Matrix
  • Caenorhabditis elegans
  • Basement Membrane
  • Animals
 

Citation

APA
Chicago
ICMJE
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Jayadev, R., Morais, M. R. P. T., Ellingford, J. M., Srinivasan, S., Naylor, R. W., Lawless, C., … Lennon, R. (2022). A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations. Science Advances, 8(20), eabn2265. https://doi.org/10.1126/sciadv.abn2265
Jayadev, Ranjay, Mychel R. P. T. Morais, Jamie M. Ellingford, Sandhya Srinivasan, Richard W. Naylor, Craig Lawless, Anna S. Li, et al. “A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations.Science Advances 8, no. 20 (May 2022): eabn2265. https://doi.org/10.1126/sciadv.abn2265.
Jayadev R, Morais MRPT, Ellingford JM, Srinivasan S, Naylor RW, Lawless C, et al. A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations. Science advances. 2022 May;8(20):eabn2265.
Jayadev, Ranjay, et al. “A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations.Science Advances, vol. 8, no. 20, May 2022, p. eabn2265. Epmc, doi:10.1126/sciadv.abn2265.
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. A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations. Science advances. 2022 May;8(20):eabn2265.

Published In

Science advances

DOI

EISSN

2375-2548

ISSN

2375-2548

Publication Date

May 2022

Volume

8

Issue

20

Start / End Page

eabn2265

Related Subject Headings

  • Zebrafish
  • Humans
  • Extracellular Matrix Proteins
  • Extracellular Matrix
  • Caenorhabditis elegans
  • Basement Membrane
  • Animals