Scribble promotes alveologenesis in the pregnant mammary gland for milk production

Abstract

Mammary glands are comprised of ducts and terminal lobules that form tree-like structures. Luminal epithelial cells in these lobules undergo differentiation into alveolar cells in pregnancy to support milk production. This study reveals that Scribble (SCRIB), a scaffold protein expressed in progesterone receptor (PGR)-positive cells, plays a critical role in mammary gland alveologenesis in mice. We conditionally deleted Scrib using a Pgr-Cre driver. PGR is heterogeneously expressed throughout the luminal epithelium. Scrib loss in mammary glands by Pgr-Cre (Scribf/fPgrCre/+) shows inefficient alveologenesis and terminal end bud (TEB)-like morphology during pregnancy, resulting in poor milk production and subsequent death of pups after delivery. The differentiation of PGR-positive epithelial cells into Elf5-expressing alveolar cells is defective in Scribf/fPgrCre/+ mice. These changes are reflected in reduced activation of JAK2 and PAK1, resulting in downregulation of pSTAT5, a critical transcriptional factor for alveologenesis. These results provide evidence that SCRIB impacts PGR-positive cell lineage during alveologenesis, which impacts milk production and the health of offspring.

Whole-Genome Sequencing of Endangered Dengchuan Cattle Reveals Its Genomic Diversity and Selection Signatures

“…Furthermore, PTPN12 is a protein tyrosine phosphatase that contributes to the stable 3D acinar formation of mammary epithelial cells ( Sun et al, 2011 ). PGR promotes alveologenesis in the pregnant mammary gland for milk production ( Aikawa et al, 2020 ). In addition, among the seven genes overlapped between Dengchuan cattle and Holstein cattle, we examined the scanning signal of PTDSS1 and found that the CLR value in Dengchuan cattle (∼638) was much higher than that in Holstein cattle (∼431).…”