Myocardial Mycn is essential for mouse ventricular wall morphogenesis

Cristina Harmelink, Yin Peng, Paige DeBenedittis, Hanying Chen, Weinian Shou, Kai Jiao

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

MYCN is a highly conserved transcription factor with multifaceted roles in development and disease. Mutations in MYCN are associated with Feingold syndrome, a developmental disorder characterized in part by congenital heart defects. Mouse models have helped elucidate MYCN functions; however its cardiac-specific roles during development remain unclear. We employed a Cre/. loxp strategy to uncover the specific activities of MYCN in the developing mouse myocardium. Myocardial deletion of Mycn resulted in a thin-myocardial wall defect with dramatically reduced trabeculation. The mutant heart defects strongly resemble the phenotype caused by disruption of BMP10 and Neuregulin-1 (NRG1) signaling pathways, two central mediators of myocardial wall development. Our further examination showed that expression of MYCN is regulated by both BMP and NRG1 signaling. The thin-wall defect in mutant hearts is caused by a reduction in both cell proliferation and cell size. MYCN promotes cardiomyocyte proliferation through regulating expression of cell cycle regulators (including CCND1, CCND2, and ID2) and promotes cardiomyocyte growth through regulating expression of p70S6K. In addition, expression of multiple sarcomere proteins is altered in Mycn myocardial-inactivation embryos, indicating its essential role for proper cardiomyocyte differentiation. In summary, Mycn acts downstream of BMP and NRG1 cardiogenic signaling pathways to promote normal myocardial wall morphogenesis.

Original languageEnglish
Pages (from-to)53-63
Number of pages11
JournalDevelopmental Biology
Volume373
Issue number1
DOIs
StatePublished - Jan 1 2013

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Neuregulin-1
Morphogenesis
Cardiac Myocytes
70-kDa Ribosomal Protein S6 Kinases
Sarcomeres
Congenital Heart Defects
Cell Size
Myocardium
Cell Cycle
Transcription Factors
Embryonic Structures
Cell Proliferation
Phenotype
Mutation
Growth
Proteins

Keywords

  • Cardiogenesis
  • Heart development
  • MYCN
  • Myocardial wall development
  • Trabeculation

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Cite this

Myocardial Mycn is essential for mouse ventricular wall morphogenesis. / Harmelink, Cristina; Peng, Yin; DeBenedittis, Paige; Chen, Hanying; Shou, Weinian; Jiao, Kai.

In: Developmental Biology, Vol. 373, No. 1, 01.01.2013, p. 53-63.

Research output: Contribution to journalArticle

Harmelink, Cristina ; Peng, Yin ; DeBenedittis, Paige ; Chen, Hanying ; Shou, Weinian ; Jiao, Kai. / Myocardial Mycn is essential for mouse ventricular wall morphogenesis. In: Developmental Biology. 2013 ; Vol. 373, No. 1. pp. 53-63.
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