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First published online 17 August 2005
doi: 10.1242/dev.01970

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.01970v1 132/18/4193    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Beis, D. Articles by Jungblut, B. Search for Related Content PubMed PubMed Citation Articles by Beis, D. Articles by Jungblut, B.

Genetic and cellular analyses of zebrafish atrioventricular cushion and valve development

Dimitris Beis^1,*,, Thomas Bartman^1,, Suk-Won Jin¹, Ian C. Scott¹, Leonard A. D'Amico¹, Elke A. Ober^1,, Heather Verkade¹, Julie Frantsve¹, Holly A. Field¹, Ann Wehman², Herwig Baier², Alexandra Tallafuss³, Laure Bally-Cuif³, Jau-Nian Chen⁴, Didier Y. R. Stainier^1,¶ and Benno Jungblut^1,

¹ Department of Biochemistry and Biophysics and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA
² Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA
³ Zebrafish Neurogenetics Group, IDG, GSF-National Research Center for Environment and Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany
⁴ Department of Molecular, Cellular, and Developmental Biology, University of California Los Angeles, CA 90095, USA

^¶ Author for correspondence (didier_stainier{at}biochem.ucsf.edu)

Accepted 7 July 2005

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.

Key words: Heart, AV canal, Endocardium, Notch, Calcineurin, Zebrafish

Related articles in Development:

Heart valve development: from genes to cells

Development 2005 132: e1805. [Full Text]  

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