PUBLICATION
A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations
- Authors
- Jayadev, R., Morais, M.R.P.T., Ellingford, J.M., Srinivasan, S., Naylor, R.W., Lawless, C., Li, A.S., Ingham, J.F., Hastie, E., Chi, Q., Fresquet, M., Koudis, N.M., Thomas, H.B., O'Keefe, R.T., Williams, E., Adamson, A., Stuart, H.M., Banka, S., Smedley, D., Genomics England Research Consortium, Sherwood, D.R., Lennon, R.
- ID
- ZDB-PUB-220519-10
- Date
- 2022
- Source
- Science advances 8: eabn2265 (Journal)
- Registered Authors
- Lennon, Rachel, Naylor, Richard
- Keywords
- none
- MeSH Terms
-
- Extracellular Matrix/genetics
- Extracellular Matrix/metabolism
- Humans
- Caenorhabditis elegans*/genetics
- Caenorhabditis elegans*/metabolism
- PubMed
- 35584218 Full text @ Sci Adv
Abstract
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.
Genes / Markers
Figure Gallery (8 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping