Foxc2 is required for proper cardiac neural crest cell migration, outflow tract septation, and ventricle expansion. Issue 12 (30th November 2018)

• Record Type: Journal Article
• Authors: Inman, Kimberly E.; Caiaffa, Carlo Donato; Melton, Kristin R.; Sandell, Lisa L.; Achilleos, Annita; Kume, Tsutomu; Trainor, Paul A.
• Is Part Of: Developmental dynamics. Volume 247:Issue 12(2018)
• Page Start: 1286
• Page End: 1296
• Publication Date: 2018-11-30
• Subjects: Foxc2 -- cardiac neural crest -- outflow tract -- heart development -- persistent truncus arteriosus -- common arterial trunk; Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.24684
• Languages: English
• ISSNs: 1058-8388

Abstract

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. Key Findings: Foxc2 is expressed in migrating neural crest cells and cardiac mesenchyme. On the 129s6/SvEv genetic background, Foxc2 loss‐of‐function embryos exhibit persistent truncus arteriosus and ventricle hypoplasia, leading to embryonic lethality at E13.5. Aberrant cardiac neural crest migration in association with disruption in guidance cues precedes reduced contribution to the outflow tract. Ventricle patterning and development is impaired in the absence of Foxc2.