title: Par-1b is required for morphogenesis and differentiation of myoepithelial cells during salivary gland development.
abstract: The salivary epithelium initiates as a solid mass of epithelial cells that are organized into a primary bud that undergoes morphogenesis and differentiation to yield bilayered acini consisting of interior secretory acinar cells that are surrounded by contractile myoepithelial cells in mature salivary glands. How the primary bud transitions into acini has not been previously documented. We document here that the outer epithelial cells subsequently undergo a vertical compression as they express smooth muscle α-actin and differentiate into myoepithelial cells. The outermost layer of polarized epithelial cells assemble and organize the basal deposition of basement membrane, which requires basal positioning of the polarity protein, Par-1b. Whether Par-1b is required for the vertical compression and differentiation of the myoepithelial cells is unknown. Following manipulation of Par-1b in salivary gland organ explants, Par-1b-inhibited explants showed both a reduced vertical compression of differentiating myoepithelial cells and reduced levels of smooth muscle α-actin. Rac1 knockdown and inhibition of Rac GTPase function also inhibited branching morphogenesis. Since Rac regulates cellular morphology, we investigated a contribution for Rac in myoepithelial cell differentiation. Inhibition of Rac GTPase activity showed a similar reduction in vertical compression and smooth muscle α-actin levels while decreasing the levels of Par-1b protein and altering its basal localization in the outer cells. Inhibition of ROCK, which is required for basal positioning of Par-1b, resulted in mislocalization of Par-1b and loss of vertical cellular compression, but did not significantly alter levels of smooth muscle α-actin in these cells. Overexpression of Par-1b in the presence of Rac inhibition restored basement membrane protein levels and localization. Our results indicate that the basal localization of Par-1b in the outer epithelial cells is required for myoepithelial cell compression, and Par-1b is required for myoepithelial differentiation, regardless of its localization.
authors.affiliation: a Department of Biological Sciences , University at Albany, State University of New York , Albany , NY , USA.|b Graduate Program in Molecular, Cellular, Developmental, and Neural Biology , University at Albany, State University of New York , Albany , NY , USA.
authors.forename: Elise M
authors.initials: EM
authors.lastname: Gervais
authors.affiliation: a Department of Biological Sciences , University at Albany, State University of New York , Albany , NY , USA.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Sequeira
authors.affiliation: a Department of Biological Sciences , University at Albany, State University of New York , Albany , NY , USA.
authors.forename: Weihao
authors.initials: W
authors.lastname: Wang
authors.affiliation: a Department of Biological Sciences , University at Albany, State University of New York , Albany , NY , USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Abraham
authors.affiliation: a Department of Biological Sciences , University at Albany, State University of New York , Albany , NY , USA.
authors.forename: Janice H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: a Department of Biological Sciences , University at Albany, State University of New York , Albany , NY , USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Leonard
authors.affiliation: a Department of Biological Sciences , University at Albany, State University of New York , Albany , NY , USA.|b Graduate Program in Molecular, Cellular, Developmental, and Neural Biology , University at Albany, State University of New York , Albany , NY , USA.
authors.forename: Kara A
authors.initials: KA
authors.lastname: DeSantis
authors.affiliation: a Department of Biological Sciences , University at Albany, State University of New York , Albany , NY , USA.
authors.forename: Melinda
authors.initials: M
authors.lastname: Larsen
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D016764:Cell Polarity; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012469:Salivary Glands / Q000166:cytology* / Q000196:embryology*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C122043:Mark2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020744:rac GTP-Binding Proteins
keywords: Par-1b; ROCK; Rac1; apicobasal polarity; branching morphogenesis; differentiation; myoepithelial cells; submandibular gland