Lumen formation during mammary epithelial morphogenesis: insights from in vitro and in vivo models.

The mammary gland undergoes a morphogenetic program during embryogenesis and puberty that leads to the development of hollow ductal system terminating in acinar units. It later expands to generate an elaborate network to deliver milk to newborn progeny. Previous studies in our laboratory using three-dimensional basement membrane cultures of mammary epithelial cells, in which acini-like structures form from single cells, have indicated that lumen formation requires clearance of the cells in the center of the acini by apoptosis. This apoptotic program in vitro requires the pro-death mediator BIM. Recently we found that BIM is also required in the mouse mammary gland for apoptosis during lumen formation, which correlates the 3D acinar model to mammary morphogenesis in vivo. Herein we put into perspective the relevance of our in vitro and in vivo findings to discuss luminal space formation and maintenance during mammary morphogenesis.