Laminin Alpha 5 Regulates Mammary Gland Remodeling Through Luminal Cell Differentiation and Wnt4-mediated Epithelial Crosstalk

Overview

Journal Development

Specialty Biology

Date 2021 Jun 15

PMID 34128985

Citations 6

Authors

Johanna I Englund

Alexandra Ritchie

Leander Blaas

Hanne Cojoc

Nalle Pentinmikko

Julia Dohla

Sharif Iqbal

Manuel Patarroyo

Pekka Katajisto

Affiliations

Soon will be listed here.

Abstract

Epithelial attachment to the basement membrane (BM) is essential for mammary gland development, yet the exact roles of specific BM components remain unclear. Here, we show that Laminin α5 (Lama5) expression specifically in the luminal epithelial cells is necessary for normal mammary gland growth during puberty, and for alveologenesis during pregnancy. Lama5 loss in the keratin 8-expressing cells results in reduced frequency and differentiation of hormone receptor expressing (HR+) luminal cells. Consequently, Wnt4-mediated crosstalk between HR+ luminal cells and basal epithelial cells is compromised during gland remodeling, and results in defective epithelial growth. The effects of Lama5 deletion on gland growth and branching can be rescued by Wnt4 supplementation in the in vitro model of branching morphogenesis. Our results reveal a surprising role for BM-protein expression in the luminal mammary epithelial cells, and highlight the function of Lama5 in mammary gland remodeling and luminal differentiation.

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