Unknown

Dataset Information

0

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.

SUBMITTER: Aikawa S 

PROVIDER: S-EPMC7241298 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7612858 | biostudies-literature
| S-EPMC7887553 | biostudies-literature
| S-EPMC4926316 | biostudies-literature
| S-EPMC5856648 | biostudies-literature
| S-EPMC4604487 | biostudies-literature
| S-EPMC6465250 | biostudies-literature
| S-EPMC6196465 | biostudies-literature
| S-EPMC3871720 | biostudies-literature
| S-EPMC6386411 | biostudies-literature
| S-EPMC8369411 | biostudies-literature