Scribble promotes alveologenesis in the pregnant mammary gland for milk production

Author:

Aikawa Shizu12,Yuan Jia12,Dewar Amanda12,Sun Xiaofei12,Dey Sudhansu K12

Affiliation:

1. 1Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

2. 2College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA

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.

Publisher

Bioscientifica

Subject

Cell Biology,Obstetrics and Gynaecology,Endocrinology,Embryology,Reproductive Medicine

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