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Development. 2014 Aug;141(15):3040-9. doi: 10.1242/dev.106518. Epub 2014 Jul 3.

Congenital heart disease protein 5 associates with CASZ1 to maintain myocardial tissue integrity.

Author information

1
University of North Carolina McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA Department of Biology, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA.
2
University of North Carolina McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA Department of Genetics, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA.
3
Department of Biology, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA.
4
University of North Carolina McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA Department of Biology, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA Department of Genetics, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA frank_conlon@med.unc.edu.

Abstract

The identification and characterization of the cellular and molecular pathways involved in the differentiation and morphogenesis of specific cell types of the developing heart are crucial to understanding the process of cardiac development and the pathology associated with human congenital heart disease. Here, we show that the cardiac transcription factor CASTOR (CASZ1) directly interacts with congenital heart disease 5 protein (CHD5), which is also known as tryptophan-rich basic protein (WRB), a gene located on chromosome 21 in the proposed region responsible for congenital heart disease in individuals with Down's syndrome. We demonstrate that loss of CHD5 in Xenopus leads to compromised myocardial integrity, improper deposition of basement membrane, and a resultant failure of hearts to undergo cell movements associated with cardiac formation. We further report that CHD5 is essential for CASZ1 function and that the CHD5-CASZ1 interaction is necessary for cardiac morphogenesis. Collectively, these results establish a role for CHD5 and CASZ1 in the early stages of vertebrate cardiac development.

KEYWORDS:

CASTOR; CASZ1; CHD5; Cardiac; Cardiomyocyte; Congenital heart disease; Down's syndrome; Heart development; Heart morphogenesis; Morphogenesis; Proliferation; WRB; Xenopus

PMID:
24993940
PMCID:
PMC4197678
DOI:
10.1242/dev.106518
[Indexed for MEDLINE]
Free PMC Article

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