Meeting Abstract
37.5 Sunday, Jan. 5 09:00 Targeted cell cycle arrest halts basement membrane gap expansion during nematode uterine-vulval attachment MATUS, DQ*; CHANG, E; MAKOHON-MOORE, SC; SHERWOOD, DR; Duke University; Duke University; Duke University; Duke University david.matus@duke.edu
The creation of large gaps in basement membranes (BM) is a critical component of tissue construction and normal physiology, as well as disease states such as cancer. Still, how large BM breaks are generated and stabilized remains poorly understood. C. elegans uterine-vulval attachment is a visually and experimentally tractable model to elucidate mechanisms underlying BM gap formation. During C. elegans larval development the gonadal anchor cell (AC) breaches the BM and initiates a connection between the uterine and vulval tissues. Following invasion, the vulval cells invaginate and expand, generating forces that widen the gap in the BM. The BM moves past the dividing vulE and vulF cells and stabilizes, in an integrin-dependent manner, over the post-mitotic vulD cell. To understand the evolution of the mechanisms that underlie BM gap formation we have examined uterine-vulval attachment in twenty species of rhabditid nematodes, representing several hundred million years of evolution. We find that in all nematodes surveyed, the AC breaches the BM, initiating uterine-vulval attachment. Strikingly, the expanding BM gap always stabilizes over the post-mitotic vulD cell, the only vulval cell across rhabditid nematodes that never divides. In C. elegans, we find that causing excess divisions of vulD expands the BM gap, and inhibition of the interior vulE and vulF divisions contracts it. Visualization of the cell-BM interaction reveals that dividing vulval cells lose BM contact, allowing the BM gap to expand. Finally, we show that this integrin-dependent adhesion is directed by a concentration of laminin at the lip of the BM gap. Together, our studies reveal a new mechanism for stabilizing expanding BM gaps by using targeted cell cycle exit and BM gap-mediated integrin localization.
