During mammary gland development, mammary epithelial tissue undergoes branching morphogenesis to invade the surrounding mammary fat pad. Morphologically, the gland is relatively simple at birth, but undergoes dramatic remodelling during puberty. Based primarily on work in vitro, the matrix metalloproteases MMP14 (MT1-MMP) and MMP15 (MT2-MMP) are thought to play key roles in this branching morphogenesis, both through protease-dependent remodelling of the extracellular matrix and through protease-independent mechanisms. By analysing early (prepubertal) postnatal mammary gland development in mice (p. 3956), Stephen Weiss and colleagues now challenge this model. They find that, in contrast to in vitro data, global deletion of MMP14 or MMP15 has no significant effect on this phase of mammary gland branching, casting doubt on the degree to which proteinase-mediated extracellular matrix remodelling is required for this morphogenetic event. However, the authors also uncover unexpected and differential roles for the two MMPs in adipose development: MMP14 deletion impairs white fat differentiation, while MMP15 mutants show enhanced beige/brown fat formation. The mechanisms underlying this remain unclear, but these data suggest that current models of the roles of these MMPs in mammary gland development may need revising.
