Cardiac neural crest and outflow tract defects in Lrp6 mutant mice

Lanying Song, Yunhong Li, Kai Wang, Chengji Zhou

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The role of a key Wnt coreceptor Lrp6 during heart development remains unclear. Here we show that ablation of Lrp6 in mice causes conotruncal anomalies including double-outlet right ventricle (DORV), outflow tract (OFT) cushion hypoplasia, and ventricular septal defect (VSD). Cardiac neural crest cells are specifically lost in the dorsal neural tube and caudal pharyngeal arches of the mutant embryos. We also demonstrate that Lrp6 is required for proliferation and survival of cardiac progenitors and for the expression of Isl1 in the secondary heart field. Other known cardiogenic regulators such as Msx1, Msx2, and Fgf8 are also significantly diminished in the mutant pharyngeal arches and/or OFT. Unexpectedly, the myocardium differentiation factors Mef2c and Myocardin are upregulated in the mutant OFT. Our results indicate that Lrp6 is essential for cardiac neural crest and OFT development upstream of multiple important cardiogenic genes in different cardiac lineage cells during early cardiogenesis.

Original languageEnglish (US)
Pages (from-to)200-210
Number of pages11
JournalDevelopmental Dynamics
Volume239
Issue number1
DOIs
StatePublished - Jan 2010

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Keywords

  • Bmp4
  • Cardiac neural crest (CNC)
  • Congenital heart defects (CHD)
  • Double outflow right ventricle (DORV)
  • Fgf8
  • Isl1
  • Lrp6 mutant mice
  • Mef2c
  • Msx1
  • Msx2
  • Outflow tract (OFT)
  • Pax3
  • Pharyngeal arch (PA)
  • Secondary heart field (SHF)
  • Tcfap2a (AP-2alpha)
  • Ventricular septal defects (VSD)
  • Wnt/beta-catenin signaling

ASJC Scopus subject areas

  • Developmental Biology

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