Parasympathetic innervation regulates tubulogenesis in the developing salivary gland

Pavel I Nedvetsky, Elaine Emmerson, Jennifer K Finley, Andreas Ettinger, Noel Cruz-Pacheco, Jan Prochazka, Candace L Haddox, Emily Northrup, Craig Hodges, Keith E Mostov, Matthew P Hoffman, Sarah M Knox

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)449-62
Number of pages14
JournalDevelopmental Cell
Volume30
Issue number4
DOIs
Publication statusPublished - 25 Aug 2014

Keywords

  • Animals
  • Apoptosis
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Epithelial Cells
  • Ganglia, Parasympathetic
  • Mice
  • Mice, Inbred ICR
  • Organogenesis
  • Salivary Ducts
  • Vasoactive Intestinal Peptide
  • Journal Article
  • Research Support, N.I.H., Extramural

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