Planar cell polarity signaling regulates polarized second heart field morphogenesis to promote both arterial and venous pole septation

Development. 2019 Oct 9;146(20):dev181719. doi: 10.1242/dev.181719.

Abstract

The second heart field (SHF) harbors progenitors that are important for heart formation, but little is known about its morphogenesis. We show that SHF population in the mouse splanchnic mesoderm (SpM-SHF) undergoes polarized morphogenesis to preferentially elongate anteroposteriorly. Loss of Wnt5, a putative ligand of the planar cell polarity (PCP) pathway, causes the SpM-SHF to expand isotropically. Temporal tracking reveals that the Wnt5a lineage is a unique subpopulation specified as early as E7.5, and undergoes bi-directional deployment to form specifically the pulmonary trunk and the dorsal mesenchymal protrusion (DMP). In Wnt5a-/- mutants, Wnt5a lineage fails to extend into the arterial and venous poles, leading to both outflow tract and atrial septation defects that can be rescued by an activated form of PCP effector Daam1. We identify oriented actomyosin cables in the medial SpM-SHF as a potential Wnt5a-mediated mechanism that promotes SpM-SHF lengthening and restricts its widening. Finally, the Wnt5a lineage also contributes to the pulmonary mesenchyme, suggesting that Wnt5a/PCP is a molecular circuit recruited by the recently identified cardiopulmonary progenitors to coordinate morphogenesis of the pulmonary airways and the cardiac septations necessary for pulmonary circulation.This article has an associated 'The people behind the papers' interview.

Keywords: Morphogenesis; Planar cell polarity; Second heart field.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Polarity / drug effects*
  • Female
  • Immunohistochemistry
  • Male
  • Mesoderm / cytology
  • Mesoderm / drug effects
  • Mice
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Morphogenesis / drug effects*
  • Signal Transduction / drug effects*
  • Tamoxifen / pharmacology
  • Wnt-5a Protein / genetics
  • Wnt-5a Protein / metabolism*
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism

Substances

  • Microfilament Proteins
  • Wnt-5a Protein
  • Wnt5a protein, mouse
  • Tamoxifen
  • Daam1 protein, mouse
  • rho GTP-Binding Proteins