Genetic and cellular analyses of zebrafish atrioventricular cushion and valve development

被引:519
作者
Beis, D
Bartman, T
Jin, SW
Scott, IC
D'Amico, LA
Ober, EA
Verkade, H
Frantsve, J
Field, HA
Wehman, A
Baier, H
Tallafuss, A
Bally-Cuif, L
Chen, JN
Stainier, DYR [1 ]
Jungblut, B
机构
[1] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA
[4] IDG, GSF, Natl Res Ctr Environm & Hlth, Zebrafish Neurogenet Grp, D-85764 Neuherberg, Germany
[5] Univ Calif Los Angeles, Dept Mol Cellular & Dev Biol, Los Angeles, CA 90095 USA
来源
DEVELOPMENT | 2005年 / 132卷 / 18期
关键词
heart; AV canal; endocardium; Notch; Calcineurin; zebrafish;
D O I
10.1242/dev.01970
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Defects in cardiac valve morphogenesis and septation of the heart chambers constitute some of the most common human congenital abnormalities. Some of these defects originate from errors in atrioventricular (AV) endocardial cushion development. Although this process is being extensively studied in mouse and chick, the zebrafish system presents several advantages over these models, including the ability to carry out forward genetic screens and study vertebrate gene function at the single cell level. In this paper, we analyze the cellular and subcellular architecture of the zebrafish heart during stages of AV cushion and valve development and gain an unprecedented level of resolution into this process. We find that endocardial cells in the AV canal differentiate morphologically before the onset of epithelial to mesenchymal transformation, thereby defining a previously unappreciated step during AV valve formation. We use a combination of novel transgenic lines and fluorescent immunohistochemistry to analyze further the role of various genetic (Notch and Calcineurin signaling) and epigenetic (heart function) pathways in this process. In addition, from a large-scale forward genetic screen we identified 55 mutants, defining 48 different genes, that exhibit defects in discrete stages of AV cushion development. This collection of mutants provides a unique set of tools to further our understanding of the genetic basis of cell behavior and differentiation during AV valve development.
引用
收藏
页码:4193 / 4204
页数:12
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