A serendipitous convergence- insights on extracellular matrix proteoglycans and their proteolysis in ensuring successful mammalian birth.

Tissues comprise not only cells, but also extracellular matrix (ECM), which is assembled from some of the most abundant molecules in animals. ECM composition and organization underlie the tissue architecture of most organs by design and is thus optimized for their principal physiologic functions. While the structural role of ECM is widely accepted, its regulatory role is often overlooked. We identified a crucial role for ECM proteoglycans aggrecan and versican and the proteases which degrade them in ensuring dimorphism of the umbilical arteries and vein in relation to rapid closure of the umbilical arteries at birth. Another study which sought to define the roles of proteases in the vasculature, unexpectedly uncovered a requirement for ADAMTS9, a secreted protease, in trimming pericellular versican in the late-gestation myometrium. This activity was found to be necessary for priming the myometrium for sufficiently strong uterine contraction at parturition. These studies and others showed that fine tuning of umbilical vascular and myometrial ECM is crucial for survival of the species and illustrate how regulatory processes of the ECM can modulate smooth muscle cell phenotype. In addition to the outcomes, the underlying narrative illustrates how a mix of curiosity, happenstance, exploration of tangents, interdisciplinary collaboration and generous sharing of resources is rewarding and has a significant role in scientific discoveries.