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Dev Dyn. 2018 Dec;247(12):1286-1296. doi: 10.1002/dvdy.24684.

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

Author information

1
Department of Natural Sciences, Shawnee State University, Portsmouth, Ohio.
2
Stowers Institute for Medical Research, Kansas City, Missouri.
3
Section of Neonatology, Pulmonary and Perinatal Biology, Cincinnati Children's Hospital, Cincinnati, Ohio.
4
Department of Oral Immunology & Infectious Diseases, School of Dentistry, University of Louisville, Louisville, Kentucky.
5
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas.
6
Feinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
7
Department of Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, Kansas.

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. © 2018 Wiley Periodicals, Inc.

KEYWORDS:

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

PMID:
30376688
PMCID:
PMC6275097
[Available on 2019-12-01]
DOI:
10.1002/dvdy.24684

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