title: LIM kinase regulation of cytoskeletal dynamics is required for salivary gland branching morphogenesis.
abstract: Coordinated actin microfilament and microtubule dynamics is required for salivary gland development, although the mechanisms by which they contribute to branching morphogenesis are not defined. Because LIM kinase (LIMK) regulates both actin and microtubule organization, we investigated the role of LIMK signaling in mouse embryonic submandibular salivary glands using ex vivo organ cultures. Both LIMK 1 and 2 were necessary for branching morphogenesis and functioned to promote epithelial early- and late-stage cleft progression through regulation of both microfilaments and microtubules. LIMK-dependent regulation of these cytoskeletal systems was required to control focal adhesion protein-dependent fibronectin assembly and integrin β1 activation, involving the LIMK effectors cofilin and TPPP/p25, for assembly of the actin- and tubulin-based cytoskeletal systems, respectively. We demonstrate that LIMK regulates the early stages of cleft formation--cleft initiation, stabilization, and progression--via establishment of actin stability. Further, we reveal a novel role for the microtubule assembly factor p25 in regulating stabilization and elongation of late-stage progressing clefts. This study demonstrates the existence of multiple actin- and microtubule-dependent stabilization steps that are controlled by LIMK and are required in cleft progression during branching morphogenesis.
authors: Department of Biological Sciences, University at Albany, State University of New York, Albany, NY 12222.
authors: Shayoni
authors: S
authors: Ray
authors: Department of Biological Sciences, University at Albany, State University of New York, Albany, NY 12222.
authors: Joseph A
authors: JA
authors: Fanti
authors: Department of Biological Sciences, University at Albany, State University of New York, Albany, NY 12222.
authors: Diego P
authors: DP
authors: Macedo
authors: Department of Biological Sciences, University at Albany, State University of New York, Albany, NY 12222 mlarsen@albany.edu.
authors: Melinda
authors: M
authors: Larsen
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D005353:Fibronectins / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D054461:Lim Kinases / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D009024:Morphogenesis; D009924:Organ Culture Techniques; D038081:Organogenesis; D012469:Salivary Glands / Q000196:embryology*; D015398:Signal Transduction; D014404:Tubulin / Q000378:metabolism*
chemical_list: D000199:Actins; D005353:Fibronectins; D019012:Integrin beta1; D014404:Tubulin; D054461:Lim Kinases