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Mutations affecting the cardiovascular system and other internal organs in zebrafish
J N Chen1, P Haffter, J Odenthal
1Max-Planck-Institut für Entwicklungsbiologie, Tübingen, Germany. chenj@helix.mgh.harvard.edu
Insights
Researchers screened zebrafish for mutations affecting internal organs, identifying 53 cardiovascular mutations and 23 affecting liver, intestine, or kidney. This study provides genetic entry points for understanding organogenesis.
Area of Science:
- Developmental biology
- Genetics
- Zebrafish models
Background:
- Zebrafish are a valuable model organism for studying vertebrate development.
- Identifying mutations affecting organogenesis is crucial for understanding developmental processes.
Purpose of the Study:
- To screen for and characterize mutations affecting internal organ development in zebrafish.
- To identify genes involved in cardiovascular and other organ system development.
Main Methods:
- Forward genetic screen in zebrafish.
- Phenotypic analysis of developmental mutants.
- Characterization of mutations affecting heart morphogenesis and function.
Main Results:
- Identified 53 mutations affecting the cardiovascular system, including defects in heart chamber formation and function.
- Discovered mutations impacting liver, intestine, and kidney integrity.
- Detailed specific mutations causing cardia bifida, altered chamber positioning, enlarged hearts, and reduced cardiac jelly.
Conclusions:
- Zebrafish screens are effective for identifying genes controlling organ patterning and function.
- The identified mutations offer a starting point for dissecting the genetic hierarchy of organogenesis.
Abstract:
In a screen for early developmental mutants of the zebrafish, we have identified mutations specifically affecting the internal organs. We identified 53 mutations affecting the cardiovascular system. Nine of them affect specific landmarks of heart morphogenesis. Mutations in four genes cause a failure in the fusion of the bilateral heart primordia, resulting in cardia bifida. In lonely atrium, no heart venticle is visible and the atrium is directly fused to the outflow tract. In the overlooped mutant, the relative position of the two heart chambers is distorted. The heart is enormously enlarged in the santa mutant. In two mutants, scotch tape and superglue, the cardiac jelly between the two layers of the heart is significantly reduced. We also identified a number of mutations affecting the function of the heart. The mutations affecting heart function can be subdivided into two groups, one affecting heart contraction and another affecting the rhythm of the heart beat. Among the contractility group of mutants are 5 with no heart beat at all and 15 with a reduced heart beat of one or both chambers. 6 mutations are in the rhythmicity group and specifically affect the beating pattern of the heart. Mutations in two genes, bypass and kurzschluss, cause specific defects in the circulatory system. In addition to the heart mutants, we identified 23 mutations affecting the integrity of the liver, the intestine or the kidney. In this report, we demonstrate that it is feasible to screen for genes specific for the patterning or function of certain internal organs in the zebrafish. The mutations presented here could serve as an entry point to the establishment of a genetic hierarchy underlying organogenesis.