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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.

SUBMITTER: Nedvetsky PI

PROVIDER: S-EPMC4155578 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Parasympathetic innervation regulates tubulogenesis in the developing salivary gland.

Nedvetsky Pavel I PI Emmerson Elaine E Finley Jennifer K JK Ettinger Andreas A Cruz-Pacheco Noel N Prochazka Jan J Haddox Candace L CL Northrup Emily E Hodges Craig C Mostov Keith E KE Hoffman Matthew P MP Knox Sarah M SM

Developmental cell 20140801 4

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 ...[more]

PMID: 25158854

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Project description:It has been shown that removal of parasympathetic innervation to the lacrimal gland (LG) leads to rapid reduction in tear flow. Additionally, removal of the neural input resulted in disorganization of LG structure and changes in the expression of genes associated with the secretory pathway and inflammation. The goal of this study was to investigate the change in pro-inflammatory and pro-apoptotic gene expression in the rat LG following parasympathetic denervation. Male Long-Evans rats underwent unilateral sectioning of the greater superficial petrosal nerve and were sacrificed 7 days or 2.5 months later. cDNA was synthesized from LG RNA from the contralateral control (Ctla) and parasympathectomized (Px) glands and comparative real-time PCR was performed. Mean threshold cycles (MC(T)) for the Ctla and Px LG genes were normalized to 18S rRNA MC(T) values, and the relative fold change was calculated for each gene using the 2(-DeltaDeltaC)(T) method. The expression of nuclear factor kappa B1, caspase 1, eotaxin, leukocyte antigen MRC-OX44, allograft inflammatory factor-1, MHC class II molecules RT.1B and RT.1D, IgG receptor FcRn, and macrophage metalloelastase was increased and remained elevated in the Px LG, compared with the Ctla LG. Increased expression of the initiator of apoptosis gene, caspase 2, was confirmed, but expression of the executor gene, caspase 6, was not elevated in the Px LG. Reduced expression of genes associated with post-translational protein processing-furin convertase, protein disulfide isomerase, and UDP-gal transporter isozyme 1-was noted in the Px LG. No significant changes in the expression of genes associated with lysosomal and non-lysosomal-mediated protein degradation were found. Removal of parasympathetic input may lead to decreased capacity for protein synthesis and elevated immune responses in the Px LG. These changes occur without increases in expression of the muscarinic acetylcholine receptor subtype 3, and may suggest the early changes in LG acinar cells and the pathophysiology of autoimmune responses.

Dataset Information

Parasympathetic innervation regulates tubulogenesis in the developing salivary gland.

Publications

Parasympathetic innervation regulates tubulogenesis in the developing salivary gland.

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