The fruit fly 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 (UC San Francisco) who then isolated and characterized two temperature-sensitive mutant alleles.  Our laboratory later isolated two null alleles of Drosophila Myb.  Studies of these mutants showed that aberrant cell divisions occur in the absence of Myb protein.  Myb-deficient cells exhibit a variety of mitotic defects including abnormal chromosome condensation, chromosome number (ploidy), spindle assembly, chromosome attachment to the spindle, centrosome number, and cytokinesis.  Myb null mutant animals die as late third instar larvae, a time during development when the imaginal discs that give rise to many adult tissues undergo rapid cell proliferation.

Fly life cycle image from FlyMove.  Mutant phenotype analysis adapted from Gary Larson.

The Drosophila Myb protein is localized within the cell nucleus and concentrates on DNA both in mitotically proliferating cells and in endocycling cells that lack an M phase.  In mitotically cycling cells the Myb protein localizes to euchromatin (decondensed regions of the chromosomes) but not to heterochromatin (highly condensed regions of the chromosomes).

Manak, et al, Nature Cell Biology 2007.

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, a model for site-specific DNA replication in higher eukaryotes. However, studies using mosaic analysis and compartment-specific rescue showed that Myb is not absolutely required for DNA replication in mitotically proliferating cells.  The absence of Myb did result in a failure of the normal progression of chromosome condensation, in that heterochromatin but not euchromatin condensed properly.  The cell cycle arrest that occurs in the absence of Myb can be rescued by ectopic expression of a Myb cDNA under control of the yeast GAL4 transcriptional activator.

Manak, et al, PNAS 2002; Manak, et al, Nature Cell Biology 2007