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Alveolar progenitor differentiation and lactation depends on paracrine inhibition of notch via ROBO1/CTNNB1/JAG1.
- Source :
-
Development (Cambridge, England) [Development] 2021 Nov 01; Vol. 148 (21). Date of Electronic Publication: 2021 Nov 10. - Publication Year :
- 2021
-
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.<br />Competing Interests: Competing interests L.H., O.C. and S.C. have applied for patents related to this paper. L.H. receives research funding from Zoetis Inc. C.S. and J.W.B., are employees of Zoetis Inc.<br /> (© 2021. Published by The Company of Biologists Ltd.)
- Subjects :
- Animals
Cell Line
Epithelial Cells cytology
Epithelial Cells metabolism
Epithelium metabolism
Female
Gene Expression Regulation, Developmental
Jagged-1 Protein genetics
Mammary Glands, Animal cytology
Mammary Glands, Animal physiology
Mice
Nerve Tissue Proteins genetics
Paracrine Communication
Receptors, Immunologic genetics
Signal Transduction
Stem Cells metabolism
beta Catenin genetics
Roundabout Proteins
Cell Differentiation physiology
Jagged-1 Protein metabolism
Lactation psychology
Nerve Tissue Proteins metabolism
Receptors, Immunologic metabolism
Receptors, Notch metabolism
Stem Cells cytology
beta Catenin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 148
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 34758082
- Full Text :
- https://doi.org/10.1242/dev.199940