EMBRYONIC LETHALITY CAUSED BY MUTATIONS IN BASEMENT-MEMBRANE COLLAGEN OF C-ELEGANS

BASEMENT membranes are specialized forms of extracellular matrix with important functions in development 1-3. A major structural component of basement membranes is type IV collagen, a heterotrimer of two alpha-1(IV) and one alpha-2(IV) chains, which forms a complex, polygonal network associated with other basement membrane components 4,5. Here we report that the alpha-1(IV) collagen chain of Caenorhabditis elegans is encoded by the genetic locus emb-9. Mutations in emb-9 cause temperature-sensitive lethality during late embryogenesis. We have identified single nucleotide alterations that substitute glutamic acid for glycine in the triple-helical Gly-X-Y repeat region of the alpha-1(IV) collagen in three emb-9 mutant strains. These results are direct evidence that defects in basement membranes can disrupt embryonic development and form a basis for the genetic analysis of basement membrane function.