BIM Regulates Apoptosis during Mammary Ductal Morphogenesis, and Its Absence Reveals Alternative Cell Death Mechanisms

Abstract

The adult, virgin mammary gland is a highly organized tree-like structure formed by ducts with hollowed lumen. Although lumen formation during pubertal development appears to involve apoptosis, the molecular mechanisms that regulate this process are not known. Here, we demonstrate that disruption of the BH3-only proapoptotic factor Bim in mice prevents induction of apoptosis in and clearing of the lumen in terminal end buds during puberty. However, cells that fill the presumptive luminal space are eventually cleared from the adjacent ducts by a caspase-independent death process. Within the filled Bim-/- ducts, epithelial cells are deprived of matrix attachment and undergo squamous differenti..