title: An Essential Role for Cdc42 in the Functioning of the Adult Mammary Gland.
abstract: The Rho family small GTPase Cdc42 has been implicated in a wide range of cellular functions including the establishment of cell polarity and the remodeling of the actin cytoskeletal architecture, resulting in the tight regulation of cell growth and survival during developmental processes. The complete knock-out of Cdc42 in the mouse is embryonic-lethal, and its targeted deletion in various tissues has been shown to disrupt tissue homeostasis. Thus far, in most studies, the targeted deletion of Cdc42 occurred during embryogenesis. Here, we have used a conditional gene deletion strategy in mice to probe the specific role of Cdc42 during adult mammary gland function. Cdc42 conditional-knock-out females were unable to adequately nourish their pups, due to a disorganized epithelial compartment within their mammary glands. A closer examination showed that their mammary epithelial cells were not able to maintain functional alveolar lumens, due to an inability to establish normal apical/basal epithelial polarity, as well as proper cell-cell contacts. Loss of these essential epithelial characteristics led to a premature sloughing off of the Cdc42-null epithelial cells. Overall our findings demonstrate that Cdc42 plays essential roles in mammary gland function post pregnancy, where it helps to establish proper epithelial cell polarity and tissue homeostasis during lactation.
authors.affiliation: From the Departments of Molecular Medicine, College of Veterinary Medicine, and.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Druso
authors.affiliation: From the Departments of Molecular Medicine, College of Veterinary Medicine, and.
authors.forename: Makoto
authors.initials: M
authors.lastname: Endo
authors.affiliation: From the Departments of Molecular Medicine, College of Veterinary Medicine, and.
authors.forename: Miao-Chong Joy
authors.initials: MC
authors.lastname: Lin
authors.affiliation: From the Departments of Molecular Medicine, College of Veterinary Medicine, and.
authors.forename: Xu
authors.initials: X
authors.lastname: Peng
authors.affiliation: From the Departments of Molecular Medicine, College of Veterinary Medicine, and.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Antonyak
authors.affiliation: From the Departments of Molecular Medicine, College of Veterinary Medicine, and.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Meller
authors.affiliation: From the Departments of Molecular Medicine, College of Veterinary Medicine, and Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853 rac1@cornell.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cerione
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D007774:Lactation / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C581598:Cdc42 protein, mouse; D020764:cdc42 GTP-Binding Protein
keywords: CDC42; cell polarity; mammary gland; signal transduction; signaling