Alveolar Progenitor Differentiation and Lactation Depends on Paracrine Inhibition of Notch Via ROBO1/CTNNB1/JAG1

Overview

Journal Development

Specialty Biology

Date 2021 Nov 10

PMID 34758082

Citations 4

Authors

Oscar Cazares

Sharmila Chatterjee

Pinky Lee

Catherine Strietzel

J W Bubolz

Gwyndolen Harburg

Jon Howard

Sol Katzman

Jeremy Sanford

Lindsay Hinck

Affiliations

Soon will be listed here.

Abstract

In the mammary gland, how alveolar progenitor cells are recruited to fuel tissue growth with each estrus cycle and pregnancy remains poorly understood. Here, we identify a regulatory pathway that controls alveolar progenitor differentiation and lactation by governing Notch activation in mouse. Loss of Robo1 in the mammary gland epithelium activates Notch signaling, which expands the alveolar progenitor cell population at the expense of alveolar differentiation, resulting in compromised lactation. ROBO1 is expressed in both luminal and basal cells, but loss of Robo1 in basal cells results in the luminal differentiation defect. In the basal compartment, ROBO1 inhibits the expression of Notch ligand Jag1 by regulating β-catenin (CTNNB1), which binds the Jag1 promoter. Together, our studies reveal how ROBO1/CTTNB1/JAG1 signaling in the basal compartment exerts paracrine control of Notch signaling in the luminal compartment to regulate alveolar differentiation during pregnancy.

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