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Drosophila Myb

    The fruitfly Drosophila melanogaster is widely used as a model system because of the powerful genetic, genomic, and cytological methods available in this organism, the high degree of similarity of its genes to those of humans, and the lack of redundancy in many gene families.  The sole Drosophila Myb gene was discovered by Alisa Katzen and Mike Bishop who then described two temperature-sensitive alleles (1,2).

    We ourselves isolated two null alleles of Drosophila Myb (3).  Studies of these mutants showed that in the absence of Myb function, cells undergo mitotic arrest with alterations in chromosome number (ploidy) and mitotic spindles.  The normal Myb protein is concentrated on actively replicating DNA in both mitotically cycling and in endocycling cells that lack an M phase.  These results suggested Myb might be required for DNA replication. Consistent with this hypothesis, we collaborated with Lolli Beall and Mike Botchan (UC Berkeley) to show that Myb is required for the normal amplification of chorion genes in ovarian follicle cells, the best studied model for DNA replication in higher eukaryotes (4).

    More recently we have used mosaic analysis and compartment-specific rescue to show that Myb is not absolutely required for DNA replication in mitotically cycling cells (5).  However, absence of Myb eventually results in a failure of the normal progression of chromosome condensation, such that heterochromatin but not euchromatin condenses properly.  We also showed that vertebrate B-Myb, but neither A-Myb nor c-Myb can complement cell cycle defects in Drosophila Myb null Drosophila hemocytes.  These results imply that B-Myb is the vertebrate orthologue of Drosophila Myb (6).

Drosophila Myb Mutants

Absence of Myb Protein in Mutant Larvae

Abnormal Pupariation of Myb Mutants

Abnormal Mitoses in the Absence of Myb

Myb Protein Localizes to Newly Replicated DNA

Drosophila Hematopoiesis Requires Myb

Summary of Myb Mutant Phenotype

1. Katzen, A.L., Kornberg, T.B., and J.M. Bishop. 1985. "Isolation of the proto-oncogene c-myb from D. melanogaster." Cell 41: 449-456.

2. Katzen, AL, and J.M. Bishop. 1996. "myb provides an essential function during Drosophila development." Proc Natl Acad Sci USA 93: 13955-19960.

3. Manak, J., Mitiku, N., and J.S. Lipsick. 2002. "Mutation of the Drosophila homologue of the Myb protooncogene causes genomic instability." Proc. Natl. Acad. Sci. USA 99: 7438-7443. [pdf]

4. Beall, E.L., Manak, J.R., Zhou, S., Bell, M., Lipsick, J.S., and M.R. Botchan. 2002. "Role for a Drosophila Myb-containing protein complex in site-specific DNA replication." Nature 420: 833-837. [pdf].

5. Manak JR, Wen H, Van T, Andrejka L, Lipsick JS. 2007. Loss of Drosophila Myb interrupts the progression of chromosome condensation. Nat Cell Biol. 9: 581-7. 2007 [pdf].

6. Davidson CJ, Tirouvanziam R, Herzenberg LA, Lipsick JS. 2005. Functional evolution of the vertebrate Myb gene family: B-Myb, but neither A-Myb nor c-Myb, complements Drosophila Myb in hemocytes. Genetics 169: 215-29. [pdf].