Faculty Advisor

Dr. Don Kane

Department

Biological Sciences

Presentation Date

4-11-2014

Document Type

Poster

Abstract

Progression through cell division is controlled by genes that regulate the cell cycle. As of now, the way embryos control cell division to regulate organ size remains unknown. Furthermore, mutations that cause cell cycle defects in these genes are often considered to be involved in cancer pathways. Here, we show that the zebrafish specter (spr) mutant is a cell division mutant that causes mitotic abnormalities and later becomes developmentally arrested at about 20 hours of development. We mapped the spr mutation to an interval on linkage group 5, which includes the cyclin B1 gene. Cyclin B1 is necessary for the G2 to M transition of the cell cycle. Sequencing spr mutant cDNA showed that there is a nonsense mutation (C139T) in exon 2 of cyclin B1 gene. We hypothesize that the spr mutation is caused by a non-functional cyclin B1 protein; cell cycle progression and developmental abnormalities are seen as soon as maternal cyclin B1 mRNA is depleted. In situ hybridization of cyclin B1 revealed that the expression is grossly reduced in the mutant embryo at the 10-somite stage. Sytox Green staining of DNA showed nuclear fragmentation in the mutants at the 15-somite stage. Phospho histone H3 antibody staining showed that fewer cells enter mitosis in the mutants compared to the wild type embryos, and that neural stem cells do not migrate properly to the midline to divide. In situ hybridization of deltaA, a marker for neural precursors, revealed that there are fewer neural precursors in the spr mutant at the 20-somite stage. In situ hybridization of pax2a, a marker for midbrain-hindbrain boundaries, otic placode, optic stalk, pronephros and spinal interneurons, showed that there are also fewer neural precursors in the mutant at the 15-somite stage. Caspase-3 antibody staining revealed that a wild-scale apoptosis in the spr mutant occurs as early as 10 somite in the brain and tailbud, areas that first lose an optical transparency, and correlates with further development. Thus, morphological changes described in spr mutant can be explained by the mutation in the cell cycle gene and cyclin B1 seems like a really good candidate. We are now using mRNA injections to see if we can rescue the mutant, part of the proof that the specter phenotype is caused by a mutation in cyclin B1 gene.

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