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Development. 2020 Feb 17;147(4). pii: dev181552. doi: 10.1242/dev.181552.

Laminin-binding integrins are essential for the maintenance of functional mammary secretory epithelium in lactation.

Author information

1
Institut Curie, PSL Research University, CNRS, UMR144, F-75005 Paris, France.
2
Sorbonne Universités, UPMC Univ Paris 06, F-75005 Paris, France.
3
Institut Curie Genomics of Excellence (ICGex) Platform, Institut Curie, 75005 Paris, France.
4
GenoSplice Technology, F-75005 Paris, France.
5
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104/INSERM U964/ULP, F-67404 Illkirch, France.
6
Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
7
Inserm, Paris, F-75013 Paris, France.
8
Institut Curie, PSL Research University, CNRS, UMR144, F-75005 Paris, France maria-luisa.martin-faraldo@curie.fr.

Abstract

Integrin dimers α3/β1, α6/β1 and α6/β4 are the mammary epithelial cell receptors for laminins, which are major components of the mammary basement membrane. The roles of specific basement membrane components and their integrin receptors in the regulation of functional gland development have not been analyzed in detail. To investigate the functions of laminin-binding integrins, we obtained mutant mice with mammary luminal cell-specific deficiencies of the α3 and α6 integrin chains generated using the Cre-Lox approach. During pregnancy, mutant mice displayed decreased luminal progenitor activity and retarded lobulo-alveolar development. Mammary glands appeared functional at the onset of lactation in mutant mice; however, myoepithelial cell morphology was markedly altered, suggesting cellular compensation mechanisms involving cytoskeleton reorganization. Notably, lactation was not sustained in mutant females, and the glands underwent precocious involution. Inactivation of the p53 gene rescued the growth defects but did not restore lactogenesis in mutant mice. These results suggest that the p53 pathway is involved in the control of mammary cell proliferation and survival downstream of laminin-binding integrins, and underline an essential role of cell interactions with laminin for lactogenic differentiation.

KEYWORDS:

Cre-Lox gene deletion; Differentiation; Integrin; Laminin; Mammary gland; p53

PMID:
31988184
DOI:
10.1242/dev.181552

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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