Ichabod : a maternal effect mutation disrupting organizer formation in the zebrafish / Christina Kelly.

Kelly, Christina.
x, 129 p. : ill. ; 29 cm.
Medical subjects:
Cell and Molecular Biology.
Dissertations, Academic.
Local subjects:
Penn dissertations -- Cell and molecular biology. (search)
Cell and molecular biology -- Penn dissertations. (search)
Ichabod is a zebrafish (danio rerio ) recessive maternal effect mutant, which exhibits severe anterior and dorsal deficits. Mutant embryos fail to form a morphologically normal embryonic shield or to develop head and notochord and exhibit an increase in ventrally derived structures such as ventral tail fin tissue and blood. The first molecular defect identified in ichabod mutants is the failure of beta-catenin protein to enter the YSL nuclei on the dorsal side of the mid-blastula embryo. This observation is correlated with a lack of expression of bozozok and squint, early markers of the dorsal YSL. During gastrulation, embryos exhibit marked deficits in the expression of markers of organizer and axial mesoderm while showing expansion of markers of ventral fates, indicating a dramatic reassignment of dorsoventral identity. Complete rescue of the ichabod phenotype was achieved by injection of RNAs encoding beta-catenin and presumptive downstream protein in the beta-catenin pathway. However, no measurable amelioration of the ichabod defect was obtained with RNAs encoding upstream Wnt pathway components or by proteins that affect the activity of GSK-3, suggesting that the ichabod mutation effects a step in dorsal determination independent of the regulation of beta-catenin stability by GSK-3. The genetic map position of the ichabod locus was determined using SSLP markers, allowing potential candidates to be evaluated. This work demonstrates that a maternally active gene, required for beta-catenin nuclear localization, is necessary for signaling from the YSL resulting in the formation of the dorsal organizer in zebrafish.
Supervisor: Eric S. Weinberg.
Thesis (Ph.D. in Cell and Molecular Biology) -- University of Pennsylvania, 2000.
Includes bibliographical references.
Local notes:
University Microfilms order no.: 9989610.
Weinberg, Eric S., advisor.
University of Pennsylvania.
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