Fig. 5: Proposed model detailing the phenotype of luminal Rank depleted mice and the underlying molecular mechanisms.
From: Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands
In virgin MGs, luminal Rank loss promotes an aberrant alveolar differentiation with enhanced protein synthesis and expansion of the hormone-sensing cells (PR+) that produce Rankl and lead to lactation failure. Rank-deleted parous luminal cells show a reduction in protein synthesis ability. Upon the following pregnancy, these unfit luminal cells lacking Rank cannot cope with the high translational demands required for lactation. This, together with the increased availability of Rankl for basal cells during early pregnancy, enhances Rank/NF-κB signaling in the basal cell population and activates basal bipotency in developing alveoli. Basal to luminal differentiation results in the replacement of Rank-depleted with Rank-proficient luminal cells in the alveoli to restore lactation.
