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Development, Vol 123, Issue 1 37-46, Copyright © 1996 by Company of Biologists

JOURNAL ARTICLES

A genetic screen for mutations affecting embryogenesis in zebrafish

W Driever, L Solnica-Krezel, AF Schier, SC Neuhauss, J Malicki, DL Stemple, DY Stainier, F Zwartkruis, S Abdelilah, Z Rangini, J Belak and C Boggs
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown 02129, USA. Driever@Helix.MGH.Harvard.EDU

Systematic genome-wide mutagenesis screens for embryonic phenotypes have been instrumental in the understanding of invertebrate and plant development. Here, we report the results from the first application of such a large-scale genetic screening to vertebrate development. Male zebrafish were mutagenized with N-ethyl N-nitrosourea to induce mutations in spermatogonial cells at an average specific locus rate of one in 651 mutagenized genomes. Mutations were transmitted to the F1 generation, and 2205 F2 families were raised. F3 embryos from sibling crosses within the F2 families were screened for developmental abnormalities. A total of 2337 mutagenized genomes were analyzed, and 2383 mutations resulting in abnormal embryonic and early larval phenotypes were identified. The phenotypes of 695 mutants indicated involvement of the identified loci in specific aspects of embryogenesis. These mutations were maintained for further characterization and were classified into categories according to their phenotypes. The analyses and genetic complementation of mutations from several categories are reported in separate manuscripts. Mutations affecting pigmentation, motility, muscle and body shape have not been extensively analyzed and are listed here. A total of 331 mutations were tested for allelism within their respective categories. This defined 220 genetic loci with on average 1.5 alleles per locus. For about two-thirds of all loci only one allele was isolated. Therefore it is not possible to give a reliable estimate on the degree of saturation reached in our screen; however, the number of genes that can mutate to visible embryonic and early larval phenotypes in zebrafish is expected to be several-fold larger than the one for which we have observed mutant alleles during the screen. This screen demonstrates that mutations affecting a variety of developmental processes can be efficiently recovered from zebrafish.
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B. R. Keegan, J. L. Feldman, D. H. Lee, D. S. Koos, R. K. Ho, D. Y. R. Stainier, and D. Yelon
The elongation factors Pandora/Spt6 and Foggy/Spt5 promote transcription in the zebrafish embryo
Development, January 4, 2002; 129(7): 1623 - 1632.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
R. A. Seville, S. Nijjar, M. W. Barnett, K. Masse, and E. A. Jones
Annexin IV (Xanx-4) has a functional role in the formation of pronephric tubules
Development, January 4, 2002; 129(7): 1693 - 1704.
[Abstract] [Full Text] [PDF]

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 Cold Spring Harb Symp Quant BiolHome page
D.Y.R. STAINIER, D. BEIS, B. JUNGBLUT, and T. BARTMAN
Endocardial Cushion Formation in Zebrafish
Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 49 - 56.
[Abstract] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
J. P. Briggs
The zebrafish: a new model organism for integrative physiology
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2002; 282(1): R3 - R9.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
M. Patrick Bauer and F. William Goetz
Isolation of Gonadal Mutations in Adult Zebrafish from a Chemical Mutagenesis Screen
Biol Reprod, February 1, 2001; 64(2): 548 - 554.
[Abstract] [Full Text]

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 Nucleic Acids ResHome page
J. Sprague, E. Doerry, S. Douglas, and M. Westerfield
The Zebrafish Information Network (ZFIN): a resource for genetic, genomic and developmental research
Nucleic Acids Res., January 1, 2001; 29(1): 87 - 90.
[Abstract] [Full Text] [PDF]

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 BloodHome page
T. Blake, N. Adya, C.-H. Kim, A. C. Oates, L. Zon, A. Chitnis, B. M. Weinstein, and P. P. Liu
Zebrafish homolog of the leukemia gene CBFB: its expression during embryogenesis and its relationship to scl and gata-1 in hematopoiesis
Blood, December 15, 2000; 96(13): 4178 - 4184.
[Abstract] [Full Text] [PDF]

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 Genome ResHome page
I. G. Woods, P. D. Kelly, F. Chu, P. Ngo-Hazelett, Y.-L. Yan, H. Huang, J. H. Postlethwait, and W. S. Talbot
A Comparative Map of the Zebrafish Genome
Genome Res., December 1, 2000; 10(12): 1903 - 1914.
[Abstract] [Full Text]

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 Proc. Natl. Acad. Sci. USAHome page
R. T. Peterson, B. A. Link, J. E. Dowling, and S. L. Schreiber
Small molecule developmental screens reveal the logic and timing of vertebrate development
PNAS, November 21, 2000; 97(24): 12965 - 12969.
[Abstract] [Full Text] [PDF]

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 Genome ResHome page
W. B. Barbazuk, I. Korf, C. Kadavi, J. Heyen, S. Tate, E. Wun, J. A. Bedell, J. D. McPherson, and S. L. Johnson
The Syntenic Relationship of the Zebrafish and Human Genomes
Genome Res., September 1, 2000; 10(9): 1351 - 1358.
[Abstract] [Full Text]

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 DevelopmentHome page
A. Majumdar, K. Lun, M. Brand, and I. A. Drummond
Zebrafish no isthmus reveals a role for pax2.1 in tubule differentiation and patterning events in the pronephric primordia
Development, May 15, 2000; 127(10): 2089 - 2098.
[Abstract] [PDF]

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 GeneticsHome page
Y. Imai, B. Feldman, A. F. Schier, and W. S. Talbot
Analysis of Chromosomal Rearrangements Induced by Postmeiotic Mutagenesis With Ethylnitrosourea in Zebrafish
Genetics, May 1, 2000; 155(1): 261 - 272.
[Abstract] [Full Text]

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 Hum Mol GenetHome page
A. J. Hunter, P. M. Nolan, and S. D.M. Brown
Towards new models of disease and physiology in the neurosciences: the role of induced and naturally occurring mutations
Hum. Mol. Genet., April 1, 2000; 9(6): 893 - 900.
[Abstract] [Full Text] [PDF]

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 Hum Mol GenetHome page
P. Blader and U. Strahle
Zebrafish developmental genetics and central nervous system development
Hum. Mol. Genet., April 1, 2000; 9(6): 945 - 951.
[Abstract] [Full Text] [PDF]

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 Genome ResHome page
P. D. Kelly, F. Chu, I. G. Woods, P. Ngo-Hazelett, T. Cardozo, H. Huang, F. Kimm, L. Liao, Y.-L. Yan, Y. Zhou, et al.
Genetic Linkage Mapping of Zebrafish Genes and ESTs
Genome Res., April 1, 2000; 10(4): 558 - 567.
[Abstract] [Full Text]

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 Genes Dev.Home page
W. S. Talbot and N. Hopkins
Zebrafish mutations and functional analysis of the vertebrate genome
Genes & Dev., April 1, 2000; 14(7): 755 - 762.
[Full Text]

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 Physiol. GenomicsHome page
A. C. LEKVEN, K. A. HELDE, C. J. THORPE, R. ROOKE, and R. T. MOON
Reverse genetics in zebrafish
Physiol Genomics, March 14, 2000; 2(2): 37 - 48.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
M. Halloran, M Sato-Maeda, J. Warren, F Su, Z Lele, P. Krone, J. Kuwada, and W Shoji
Laser-induced gene expression in specific cells of transgenic zebrafish
Development, January 5, 2000; 127(9): 1953 - 1960.
[Abstract] [PDF]

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 DevelopmentHome page
R. Kelsh and J. Eisen
The zebrafish colourless gene regulates development of non-ectomesenchymal neural crest derivatives
Development, January 2, 2000; 127(3): 515 - 525.
[Abstract] [PDF]

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 J. Neurosci.Home page
S.-i. Higashijima, Y. Hotta, and H. Okamoto
Visualization of Cranial Motor Neurons in Live Transgenic Zebrafish Expressing Green Fluorescent Protein Under the Control of the Islet-1 Promoter/Enhancer
J. Neurosci., January 1, 2000; 20(1): 206 - 218.
[Abstract] [Full Text] [PDF]

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 Genome ResHome page
M. Ohtsuka, S. Makino, K. Yoda, H. Wada, K. Naruse, H. Mitani, A. Shima, K. Ozato, M. Kimura, and H. Inoko
Construction of a Linkage Map of the Medaka (Oryzias latipes) and Mapping of the Da Mutant Locus Defective in Dorsoventral Patterning
Genome Res., December 1, 1999; 9(12): 1277 - 1287.
[Abstract] [Full Text]

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 Genes Dev.Home page
A. Amsterdam, S. Burgess, G. Golling, W. Chen, Z. Sun, K. Townsend, S. Farrington, M. Haldi, and N. Hopkins
A large-scale insertional mutagenesis screen in zebrafish
Genes & Dev., October 15, 1999; 13(20): 2713 - 2724.
[Abstract] [Full Text]

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 Proc. Natl. Acad. Sci. USAHome page
K. Hatta and H. Korn
Tonic inhibition alternates in paired neurons that set direction of fish escape reaction
PNAS, October 12, 1999; 96(21): 12090 - 12095.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
S. C. F. Neuhauss, O. Biehlmaier, M. W. Seeliger, T. Das, K. Kohler, W. A. Harris, and H. Baier
Genetic Disorders of Vision Revealed by a Behavioral Screen of 400 Essential Loci in Zebrafish
J. Neurosci., October 1, 1999; 19(19): 8603 - 8615.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
J. Cerdà, S. Reidenbach, S. Prätzel, and W. W. Franke
Cadherin-Catenin Complexes During Zebrafish Oogenesis: Heterotypic Junctions Between Oocytes and Follicle Cells
Biol Reprod, September 1, 1999; 61(3): 692 - 704.
[Abstract] [Full Text]

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 Proc. Natl. Acad. Sci. USAHome page
N. A. Hukriede, L. Joly, M. Tsang, J. Miles, P. Tellis, J. A. Epstein, W. B. Barbazuk, F. N. Li, B. Paw, J. H. Postlethwait, et al.
Radiation hybrid mapping of the zebrafish genome
PNAS, August 17, 1999; 96(17): 9745 - 9750.
[Abstract] [Full Text] [PDF]

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 Genome ResHome page
M. A. Gates, L. Kim, E. S. Egan, T. Cardozo, H. I. Sirotkin, S. T. Dougan, D. Lashkari, R. Abagyan, A. F. Schier, and W. S. Talbot
A Genetic Linkage Map for Zebrafish: Comparative Analysis and Localization of Genes and Expressed Sequences
Genome Res., April 1, 1999; 9(4): 334 - 347.
[Abstract] [Full Text]

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 DevelopmentHome page
K. Artinger, A. Chitnis, M Mercola, and W Driever
Zebrafish narrowminded suggests a genetic link between formation of neural crest and primary sensory neurons
Development, January 9, 1999; 126(18): 3969 - 3979.
[Abstract] [PDF]

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 DevelopmentHome page
J Malicki and W Driever
oko meduzy mutations affect neuronal patterning in the zebrafish retina and reveal cell-cell interactions of the retinal neuroepithelial sheet
Development, January 3, 1999; 126(6): 1235 - 1246.
[Abstract] [PDF]


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