Genetic and Molecular Characterization of Drosophia Brakeless: A Novel Modifier of Merlin Phenotypes
Final rept. 1 Jul 2001-30 Jun 2005
NORTH CAROLINA UNIV AT GREENSBORO
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The primary outcome of our research has been the elucidation of gene network between scribbler, Merlin and Cyclin E. We have shown that Merlin functions upstream of both scribbler and Cyclin E. We have shown that both Merlin and scribbler are dominant second site modifiers of Cyclin E phenotypes. Curiously enough, Merlin dominantly suppresses hypomorphic Cyclin E phenotypes, while, null and hypomorphic scribbler mutations dominantly enhance Cyclin E phenotypes. The two scribbler isoforms have slightly different functions the smaller SbbA expression promotes ectopic proliferationCyclin E expression, while the larger SbbB represses proliferationCyclin E expression. Using these data we have constructed an intriguing pathway for scribblerMerlin regulation of proliferation. In our model we propose that Merlin regulates the intracellular level or activity of scribbler isoforms. In undifferentiatedactively proliferating cells, the expression of the smaller, proliferagenic SbbA isoform predominate regulating gene expression. However in cells that have differentiated, Merlin may down-regulate the expression of SbbA and promote the expression of SbbB. Merlin may be regulating alternative splicing, the stabilityinstability of the mRNA or protein of scribbler isoforms, or altering the activity of sbb isoforms. However, Northern analysis clearly shows no alteration to sbb transcripts in a Merlin mutant background.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research