Numb regulates cell tension required for mammary duct elongation

Abstract

The mammary gland undergoes extensive expansion of a ductal network through the stroma during puberty and is an excellent model for understanding epithelial tube morphogenesis. To investigate a role for Numb, a multifaceted adapter protein, in epithelial tube morphogenesis, we conditionally deleted it from the mammary epithelium. We report that Numb-depletion results in altered extracellular-matrix organization, reduced cell tension, altered cell shape, and increased cell packing density, which results in a 50% reduction in mammary duct elongation. Using laser ablation in vitro and geometric-based cell force inference in vivo, we determined that Numb-deficient cells have altered cortical tension. Duct elongation defects were associated with altered E-cadherin distribution, but were independent of proliferation, apoptosis in ducts or end buds. This highlights a critical role for Numb in a mechanical mechanism that is required to maintain cell packing density during epithelial tube elongation.