The goal of this proposal is to understand the genetic mechanisms that orchestrate the events of gastrulation by characterizing zebrafish mutations that disrupt cell fates and cell rearrangements in the early embryo. This study will focus on two genes with key functions in mesoderm and endoderm development: cyclops (cyc) and enhancer of cyclops (eoc). The proposal has three specific aims: (i) to directly test the role of cyc and eoc in fate specification by tracing the fates of mesoendodermal progenitors that are disrupted in cyc:eoc mutants; (ii) to further elucidate the function of eoc by isolating and characterizing new mutations in eoc, including null mutations; (iii) to positionally clone the cyc gene in order to understand the molecular basis of its function in gastrulation and in development of the ventral neuroectoderm.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057825-05
Application #
6386928
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Greenberg, Judith H
Project Start
1998-09-01
Project End
2003-08-31
Budget Start
2001-09-01
Budget End
2003-08-31
Support Year
5
Fiscal Year
2001
Total Cost
$237,775
Indirect Cost
Name
Stanford University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
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Imai, Y; Gates, M A; Melby, A E et al. (2001) The homeobox genes vox and vent are redundant repressors of dorsal fates in zebrafish. Development 128:2407-20
Imai, Y; Talbot, W S (2001) Morpholino phenocopies of the bmp2b/swirl and bmp7/snailhouse mutations. Genesis 30:160-3
Sirotkin, H I; Dougan, S T; Schier, A F et al. (2000) bozozok and squint act in parallel to specify dorsal mesoderm and anterior neuroectoderm in zebrafish. Development 127:2583-92
Dick, A; Hild, M; Bauer, H et al. (2000) Essential role of Bmp7 (snailhouse) and its prodomain in dorsoventral patterning of the zebrafish embryo. Development 127:343-54
Feldman, B; Dougan, S T; Schier, A F et al. (2000) Nodal-related signals establish mesendodermal fate and trunk neural identity in zebrafish. Curr Biol 10:531-4
Imai, Y; Feldman, B; Schier, A F et al. (2000) Analysis of chromosomal rearrangements induced by postmeiotic mutagenesis with ethylnitrosourea in zebrafish. Genetics 155:261-72
Gritsman, K; Talbot, W S; Schier, A F (2000) Nodal signaling patterns the organizer. Development 127:921-32
Sirotkin, H I; Gates, M A; Kelly, P D et al. (2000) Fast1 is required for the development of dorsal axial structures in zebrafish. Curr Biol 10:1051-4
Talbot, W S; Schier, A F (1999) Positional cloning of mutated zebrafish genes. Methods Cell Biol 60:259-86

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