The Primary cilIum in mAmmary glaNd remodeling during the reproduction CYcle (PLIANCY) – PLIANCY

The mammary gland is a stratified epithelium made of ducts and lobulo-alveolar units that undergoes development and remodeling during the reproduction cycle. From pregnancy to lactation, steroid hormones induce proliferation and differentiation of luminal and basal cells for alveologenesis and lactation. At the end of lactation, the mammary gland regresses to go back to a quasi-virgin state, a process known as involution. It is associated with death of the majority of luminal alveolar cells, while basal cells resist to death and relocate to the ducts. Immune cells are recruited in close proximity to basal cells and clear the debris from dying luminal cells. The mechanisms that promote basal cell survival and immune cell recruitment and activation remain elusive. My preliminary data have revealed that a microtubule-based structure named the primary cilium is assembled in basal cells at involution and primary cilia promote survival of basal-like cells in vitro. Thus, we hypothesize that in the mammary gland, primary cilia promote basal cell survival which recruit and activate immune cells that clear luminal cell debris for proper tissue remodeling at involution. The PLIANCY project will directly address this hypothesis. In Aim 1, we will investigate the role of primary cilia in mammary gland involution through genetic and pharmacological perturbation of ciliogenesis at this stage, in mouse glands and organoids. In Aim 2, we will develop novel small-molecule inhibitors of ciliogenesis that will contribute to Aim 1 development and which will represent new important tools to better understand the biology of the cilium in physiology and physiopathology.