A functional circuit formed by the autonomic nerves and myofibroblasts controls mammalian alveolar formation for gas exchange

Kuan Zhang, Erica Yao, Shao An Wang, Ethan Chuang, Julia Wong, Liliana Minichiello, Andrew Schroeder, Walter Eckalbar, Paul J. Wolters, Pao Tien Chuang

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Alveolar formation increases the surface area for gas exchange. A molecular understanding of alveologenesis remains incomplete. Here, we show that the autonomic nerve and alveolar myofibroblast form a functional unit in mice. Myofibroblasts secrete neurotrophins to promote neurite extension/survival, whereas neurotransmitters released from autonomic terminals are necessary for myofibroblast proliferation and migration, a key step in alveologenesis. This establishes a functional link between autonomic innervation and alveolar formation. We also discover that planar cell polarity (PCP) signaling employs a Wnt-Fz/Ror-Vangl cascade to regulate the cytoskeleton and neurotransmitter trafficking/release from the terminals of autonomic nerves. This represents a new aspect of PCP signaling in conferring cellular properties. Together, these studies offer molecular insight into how autonomic activity controls alveolar formation. Our work also illustrates the fundamental principle of how two tissues (e.g., nerves and lungs) interact to build alveoli at the organismal level.

Original languageEnglish
Pages (from-to)1566-1581.e7
JournalDevelopmental Cell
Volume57
Issue number13
DOIs
Publication statusPublished - Jul 11 2022

Keywords

  • alveolar formation
  • autonomic nerves
  • chronic obstructive lung disease
  • contraction/migration
  • gas exchange
  • myofibroblasts
  • neurotransmitters
  • neurotrophins
  • planar cell polarity signaling
  • proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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