Foxc2 is required for proper cardiac neural crest cell migration, outflow tract septation, and ventricle expansion

Kimberly E. Inman, Carlo Donato Caiaffa, Kristin R. Melton, Lisa L. Sandell, Annita Achilleos, Tsutomu Kume, Paul A. Trainor*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: Proper development of the great vessels of the heart and septation of the cardiac outflow tract requires cardiac neural crest cells. These cells give rise to the parasympathetic cardiac ganglia, the smooth muscle layer of the great vessels, some cardiomyocytes, and the conotruncal cushions and aorticopulmonary septum of the outflow tract. Ablation of cardiac neural crest cells results in defective patterning of each of these structures. Previous studies have shown that targeted deletion of the forkhead transcription factor C2 (Foxc2), results in cardiac phenotypes similar to that derived from cardiac neural crest cell ablation. Results: We report that Foxc2-/- embryos on the 129s6/SvEv inbred genetic background display persistent truncus arteriosus and hypoplastic ventricles before embryonic lethality. Foxc2 loss-of-function resulted in perturbed cardiac neural crest cell migration and their reduced contribution to the outflow tract as evidenced by lineage tracing analyses together with perturbed expression of the neural crest cell markers Sox10 and Crabp1. Foxc2 loss-of-function also resulted in alterations in PlexinD1, Twist1, PECAM1, and Hand1/2 expression in association with vascular and ventricular defects. Conclusions: Our data indicate Foxc2 is required for proper migration of cardiac neural crest cells, septation of the outflow tract, and development of the ventricles. Developmental Dynamics 247:1286–1296, 2018.

Original languageEnglish (US)
Pages (from-to)1286-1296
Number of pages11
JournalDevelopmental Dynamics
Volume247
Issue number12
DOIs
StatePublished - Dec 2018

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Keywords

  • Foxc2
  • cardiac neural crest
  • common arterial trunk
  • heart development
  • outflow tract
  • persistent truncus arteriosus

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Inman, K. E., Caiaffa, C. D., Melton, K. R., Sandell, L. L., Achilleos, A., Kume, T., & Trainor, P. A. (2018). Foxc2 is required for proper cardiac neural crest cell migration, outflow tract septation, and ventricle expansion. Developmental Dynamics, 247(12), 1286-1296. https://doi.org/10.1002/dvdy.24684