Vangl-dependent mesenchymal thinning shapes the distal lung during murine sacculation

Sarah V. Paramore, Carolina Trenado-Yuste, Rishabh Sharan, Celeste M. Nelson, Danelle Devenport

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The planar cell polarity (PCP) complex is speculated to function in murine lung development, where branching morphogenesis generates an epithelial tree whose distal tips expand dramatically during sacculation. Here, we show that PCP is dispensable in the airway epithelium for sacculation. Rather, we find a Celsr1-independent role for the PCP component Vangl in the pulmonary mesenchyme: loss of Vangl1/2 inhibits mesenchymal thinning and expansion of the saccular epithelium. Further, loss of mesenchymal Wnt5a mimics sacculation defects observed in Vangl2-mutant lungs, implicating mesenchymal Wnt5a/Vangl signaling as a key regulator of late lung morphogenesis. A computational model predicts that sacculation requires a fluid mesenchymal compartment. Lineage-tracing and cell-shape analyses are consistent with the mesenchyme acting as a fluid tissue, suggesting that loss of Vangl1/2 impacts the ability of mesenchymal cells to exchange neighbors. Our data thus identify an explicit function for Vangl and the pulmonary mesenchyme in actively shaping the saccular epithelium.

Original languageEnglish (US)
Pages (from-to)1302-1316.e5
JournalDevelopmental cell
Volume59
Issue number10
DOIs
StatePublished - May 20 2024

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology

Keywords

  • Celsr1
  • Vangl2
  • Wnt5a
  • lung development
  • mechanical force
  • motility
  • planar cell polarity
  • sacculation
  • tissue morphodynamics

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