Development, Vol 123, Issue 1 293-302, Copyright © 1996 by Company of Biologists

JOURNAL ARTICLES

Mutations affecting the cardiovascular system and other internal organs in zebrafish

JN Chen, P Haffter, J Odenthal, E Vogelsang, M Brand, FJ van Eeden, M Furutani-Seiki, M Granato, M Hammerschmidt, CP Heisenberg, YJ Jiang, DA Kane, RN Kelsh, MC Mullins and C Nusslein-Volhard
Max-Planck-Institut fur Entwicklungsbiologie, Tubingen, Germany. chenj@helix.mgh.harvard.edu

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.
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				I. Drummond, A Majumdar, H Hentschel, M Elger, L Solnica-Krezel, A. Schier, S. Neuhauss, D. Stemple, F Zwartkruis, Z Rangini, et al. Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function Development, January 12, 1998; 125(23): 4655 - 4667. [Abstract] [PDF]

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				K. Baker, K. S. Warren, G. Yellen, and M. C. Fishman Defective "pacemaker" current (Ih) in a zebrafish mutant with a slow heart rate PNAS, April 29, 1997; 94(9): 4554 - 4559. [Abstract] [Full Text] [PDF]

				J D Molkentin, Q Lin, S A Duncan, and E N Olson Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes & Dev., April 15, 1997; 11(8): 1061 - 1072. [Abstract] [PDF]

				J. Chen, F. van Eeden, K. Warren, A Chin, C Nusslein-Volhard, P Haffter, and M. Fishman Left-right pattern of cardiac BMP4 may drive asymmetry of the heart in zebrafish Development, January 11, 1997; 124(21): 4373 - 4382. [Abstract] [PDF]

				M. Fishman and K. Chien Fashioning the vertebrate heart: earliest embryonic decisions Development, January 6, 1997; 124(11): 2099 - 2117. [Abstract] [PDF]

				P Haffter, M Granato, M Brand, M. Mullins, M Hammerschmidt, D. Kane, J Odenthal, F. van Eeden, Y. Jiang, C. Heisenberg, et al. The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio Development, January 12, 1996; 123(1): 1 - 36. [Abstract] [PDF]

				M Brand, C. Heisenberg, R. Warga, F Pelegri, R. Karlstrom, D Beuchle, A Picker, Y. Jiang, M Furutani-Seiki, F. van Eeden, et al. Mutations affecting development of the midline and general body shape during zebrafish embryogenesis Development, January 12, 1996; 123(1): 129 - 142. [Abstract] [PDF]

				F. van Eeden, M Granato, U Schach, M Brand, M Furutani-Seiki, P Haffter, M Hammerschmidt, C. Heisenberg, Y. Jiang, D. Kane, et al. Mutations affecting somite formation and patterning in the zebrafish, Danio rerio Development, January 12, 1996; 123(1): 153 - 164. [Abstract] [PDF]

				C. Heisenberg, M Brand, Y. Jiang, R. Warga, D Beuchle, F. van Eeden, M Furutani-Seiki, M Granato, P Haffter, M Hammerschmidt, et al. Genes involved in forebrain development in the zebrafish, Danio rerio Development, January 12, 1996; 123(1): 191 - 203. [Abstract] [PDF]

				Y. Jiang, M Brand, C. Heisenberg, D Beuchle, M Furutani-Seiki, R. Kelsh, R. Warga, M Granato, P Haffter, M Hammerschmidt, et al. Mutations affecting neurogenesis and brain morphology in the zebrafish, Danio rerio Development, January 12, 1996; 123(1): 205 - 216. [Abstract] [PDF]

				D. Stainier, B Fouquet, J. Chen, K. Warren, B. Weinstein, S. Meiler, M. Mohideen, S. Neuhauss, L Solnica-Krezel, A. Schier, et al. Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo Development, January 12, 1996; 123(1): 285 - 292. [Abstract] [PDF]

				M Granato, F. van Eeden, U Schach, T Trowe, M Brand, M Furutani-Seiki, P Haffter, M Hammerschmidt, C. Heisenberg, Y. Jiang, et al. Genes controlling and mediating locomotion behavior of the zebrafish embryo and larva Development, January 12, 1996; 123(1): 399 - 413. [Abstract] [PDF]

				J. Chen and M. Fishman Zebrafish tinman homolog demarcates the heart field and initiates myocardial differentiation Development, January 12, 1996; 122(12): 3809 - 3816. [Abstract] [PDF]