title: Parasympathetic innervation regulates tubulogenesis in the developing salivary gland.
abstract: A fundamental question in development is how cells assemble to form a tubular network during organ formation. In glandular organs, tubulogenesis is a multistep process requiring coordinated proliferation, polarization and reorganization of epithelial cells to form a lumen, and lumen expansion. Although it is clear that epithelial cells possess an intrinsic ability to organize into polarized structures, the mechanisms coordinating morphogenetic processes during tubulogenesis are poorly understood. Here, we demonstrate that parasympathetic nerves regulate tubulogenesis in the developing salivary gland. We show that vasoactive intestinal peptide (VIP) secreted by the innervating ganglia promotes ductal growth, leads to the formation of a contiguous lumen, and facilitates lumen expansion through a cyclic AMP/protein kinase A (cAMP/PKA)-dependent pathway. Furthermore, we provide evidence that lumen expansion is independent of apoptosis and involves the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-regulated Cl(-) channel. Thus, parasympathetic innervation coordinates multiple steps in tubulogenesis during organogenesis.
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Pavel I
authors.initials: PI
authors.lastname: Nedvetsky
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Emmerson
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Finley
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ettinger
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Noel
authors.initials: N
authors.lastname: Cruz-Pacheco
authors.affiliation: Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Prochazka
authors.affiliation: National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA.
authors.forename: Candace L
authors.initials: CL
authors.lastname: Haddox
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Northrup
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Hodges
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Keith E
authors.initials: KE
authors.lastname: Mostov
authors.affiliation: National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Hoffman
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: sarah.knox@ucsf.edu.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Knox
mesh_terms: D000818:Animals; D017209:Apoptosis; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005726:Ganglia, Parasympathetic / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D038081:Organogenesis; D018987:Salivary Ducts / Q000196:embryology* / Q000294:innervation / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases