Akhtar, N. orcid.org/0000-0002-5099-8767, Li, W., Mironov, A. et al. (1 more author) (2016) Rac1 Controls Both the Secretory Function of the Mammary Gland and Its Remodeling for Successive Gestations. Developmental Cell, 38 (5). pp. 522-535. ISSN 1534-5807
Abstract
An important feature of the mammary gland is its ability to undergo repeated morphological changes during each reproductive cycle with profound tissue expansion in pregnancy and regression in involution. However, the mechanisms that determine the tissue's cyclic regenerative capacity remain elusive. We have now discovered that Cre-Lox ablation of Rac1 in mammary epithelia causes gross enlargement of the epithelial tree and defective alveolar regeneration in a second pregnancy. Architectural defects arise because loss of Rac1 disrupts clearance in involution following the first lactation. We show that Rac1 is crucial for mammary alveolar epithelia to switch from secretion to a phagocytic mode and rapidly remove dying neighbors. Moreover, Rac1 restricts the extrusion of dying cells into the lumen, thus promoting their eradication by live phagocytic neighbors while within the epithelium. Without Rac1, residual milk and cell corpses flood the ductal network, causing gross dilation, chronic inflammation, and defective future regeneration.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | Rac1; ducts; inflammation; involution; lactation; mammary; phagocytosis; regeneration |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number WELLCOME TRUST (THE) 200588/Z/16/Z |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 21 Sep 2016 08:57 |
Last Modified: | 29 Oct 2018 09:15 |
Published Version: | http://dx.doi.org/10.1016/j.devcel.2016.08.005 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.devcel.2016.08.005 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:104939 |