DrosophilaMyt1 is a Cdk1 inhibitory kinase that regulates multiple aspects of cell cycle behavior during gametogenesis

Abstract

The metazoan Wee1-like kinases Wee1 and Myt1 regulate the essential mitotic regulator Cdk1 by inhibitory phosphorylation. This regulatory mechanism, which prevents Cdk1 from triggering premature mitotic events, is also induced during the DNA damage response and used to coordinate cell proliferation with crucial developmental events. Despite the previously demonstrated role for Myt1 regulation of Cdk1 during meiosis, relatively little is known of how Myt1 functions at other developmental stages. To address this issue, we have undertaken a functional analysis of Drosophila Myt1 that has revealed novel developmental roles for this conserved cell cycle regulator during gametogenesis. Notably, more proliferating cells were observed in myt1 mutant testes and ovaries than controls. This can partly be attributed to ectopic division of germline-associated somatic cells in myt1 mutants, suggesting that Myt1 serves a role in regulating exit from the cell cycle. Moreover, mitotic index measurements suggested that germline stem cells proliferate more rapidly, in myt1 mutant females. In addition, male myt1 germline cells occasionally undergo an extra mitotic division, resulting in meiotic cysts with twice the normal numbers of cells. Based on these observations, we propose that Myt1 serves unique Cdk1 regulatory functions required for efficient coupling of cell differentiation with cell cycle progression.

Drosophila Myt1 Is the Major Cdk1 Inhibitory Kinase for Wing Imaginal Disc Development

“…1 } genomic rescue transgene ( Jin et al 2005) and by expressing a P{UASp-dMyt1 1 } cDNA transgene (Price et al 2002) with a Neu-Gal4 transgene driver line (not shown), confirming that they were due to loss of dMyt1 activity.…”

“…Drosophila Myt1 is required for head and thoracic macrochaetae development: In a previous study of myt1 1 /Df(3L)64D-F hemizygous mutants that focused on male and female gametogenesis ( Jin et al 2005), we noted additional developmental defects affecting large sensory bristles called macrochaetae, located on the adult thorax and head. Further examination revealed similar bristle phenotypes in Df(3L)CH39/myt1 1 hemizygotes, as well as recombinant, homozygous viable myt1 1 mutants that were reisolated for this study (see materials and methods).…”

“…Genetic strains: In a previously published study of myt1 mutants, we analyzed myt1 1 /Df(3L)64D-F hemizygote and myt1 1 / myt1 2 transheterozygote genotypes (Garcia-Bellido et al 1994;Jin et al 2005). These genotypes exhibited identical gametogenesis and macrochaetae defects, indicating that myt1 1 and myt1 2 were null alleles.…”

“…These genotypes exhibited identical gametogenesis and macrochaetae defects, indicating that myt1 1 and myt1 2 were null alleles. Both of these alleles were later found to have identical mutations in the myt1 coding region, indicating they were likely preexisting mutations that were isolated on chromosomes that had subsequently acquired different secondsite lethal alleles during EMS mutagenesis ( Jin et al 2005). To make genetic manipulations easier for subsequent analysis of myt1 mutant phenotypes, we used meiotic recombination to remove secondary lethal mutations from the original myt1 1 mutant chromosome, and thereby reisolated a homozygous viable myt1 1 allele.…”

“…Whether Myt1 has a role in Drosophila oocyte maturation remains unclear (Ivanovska et al 2004), however, Drosophila myt1 mutants exhibit pleiotropic cell-cycle defects during male and female gametogenesis, which suggest that dMyt1 has a role in developmentally regulated G2 phase arrest and in cell-cycle exit mechanisms that are normally coupled with terminal differentiation (Jin et al 2005).…”