Complete focal adhesion kinase deficiency in the mammary gland causes ductal dilation and aberrant branching morphogenesis through defects in Rho kinase‐dependent cell contractility
| Autor: | Reshma A. Lalai, Bob van de Water, Hans de Bont, Martine H. van Miltenburg, Eveline van Waaij, Erik H.J. Danen, Hilary E. Beggs |
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| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Cell type Mammary gland Morphogenesis Cre recombinase Biology Biochemistry Focal adhesion Mice 03 medical and health sciences Mammary Glands Animal 0302 clinical medicine Pregnancy Internal medicine Genetics medicine Animals Lactation Molecular Biology Rho-associated protein kinase 030304 developmental biology Mice Knockout rho-Associated Kinases 0303 health sciences Myoepithelial cell Epithelial Cells Cell biology Transplantation Endocrinology medicine.anatomical_structure Focal Adhesion Kinase 1 030220 oncology & carcinogenesis Female Gene Deletion Biotechnology |
| Zdroj: | The FASEB Journal. 23:3482-3493 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | The adult, virgin mammary gland is a highly organized branched ductal network comprising two major cell types: myoepithelial and luminal epithelial cells. To study the role and mechanism of focal adhesion kinase (FAK)-mediated signaling in mammary gland development and differentiation, we used a conditional Fak-knockout mammary epithelial cell (MEC) transplantation model. Conditional Cre recombinase (Cre)-mediated Fak deletion in primary cultured MECs isolated from FAK(lox/lox)/Rosa26Cre-ERT2 donor mice caused loss of FAK in all mammary cells. Transplantation of Fak-knockout MECs in a cleared mammary fat pad of immune-deficient recipient mice resulted in development of new but dilated virgin ducts with a disrupted myoepithelial and luminal epithelial cell multilayer and aberrant ductal morphogenesis during pregnancy. In the absence of FAK, MECs spread poorly, showed enhanced Rho kinase (ROCK)-mediated cytoskeletal contractility, and failed to respond to receptor-mediated cytoskeletal remodeling. Likewise, FAK deficiency fully inhibited branching morphogenesis of mammary gland organoids in a ROCK-dependent manner. Altogether these data suggest a model in which FAK coordinates contractile forces in MECs to maintain the bilayered cellular organization of myoepithelial and luminal epithelial cells in ducts, thus allowing proper mammary gland development and function. |
| Databáze: | OpenAIRE |
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