Open AccessExpression and Function of Ccbe1 in the Chick Early Cardiogenic Regions Are Required for Correct Heart Development
Author(s) -
J. R. Furtado,
Margaret Bento,
Elizabeth Correia,
José Manuel Inácio,
José António Belo
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0115481
Subject(s) - biology , gene knockdown , heart development , in situ hybridization , progenitor cell , morpholino , microbiology and biotechnology , hemangioblast , zebrafish , gene expression , stem cell , embryonic stem cell , gene , genetics
During the course of a differential screen to identify transcripts specific for chick heart/hemangioblast precursor cells, we have identified Ccbe1 ( Collagen and calcium-binding EGF-like domain 1 ). While the importance of Ccbe1 for the development of the lymphatic system is now well demonstrated, its role in cardiac formation remained unknown. Here we show by whole-mount in situ hybridization analysis that c Ccbe1 mRNA is initially detected in early cardiac progenitors of the two bilateral cardiogenic fields (HH4), and at later stages on the second heart field (HH9-18). Furthermore, c Ccbe1 is expressed in multipotent and highly proliferative cardiac progenitors. We characterized the role of c Ccbe1 during early cardiogenesis by performing functional studies. Upon morpholino-induced c Ccbe1 knockdown, the chick embryos displayed heart malformations, which include aberrant fusion of the heart fields, leading to incomplete terminal differentiation of the cardiomyocytes. c Ccbe1 overexpression also resulted in severe heart defects, including cardia bifida. Altogether, our data demonstrate that although cardiac progenitors cells are specified in c Ccbe1 morphants, the migration and proliferation of cardiac precursors cells are impaired, suggesting that cCcbe1 is a key gene during early heart development.