The Drosophila gene morula inhibits mitotic functions in the endo cycle and the mitotic cell cycle. J.A. Wallace 1, H. Kashevsky 1, C. Lai 2, B.H. Reed 3, T.L. Orr-Weaver 1. 1) Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA; 2) Divison of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA; 3) Program in Developmental Biology, Research Institute, The Hospital for Sick Children, Toronto, Cananda.
The Drosophila morula gene acts to inhibit mitotic functions in both polyploid and mitotically dividing cells. We were able to evaluate the requirements for morula at different times in development and in different tissues using a series of mutant alleles of increasing strength. We observed the inappropriate appearance of mitotic figures in endo cycling nurse cells and ring gland cells, as well as a metaphase arrest in embryonic SM cycles and mitotically dividing larval neuroblast cells.
A regulatory role for morula in endo cycles is suggested by an increase in protein levels of the mitotic cyclin, Cyclin B, in the nurse cells. In situ hybridization studies reveal that htis increase is not due to increased levels of the transcript, but reflects post-translational regulation. Thus morula is needed to block mitosis in endo cycling cells, possibly by limiting the accumulation of mitotic cyclin proteins. It is also needed to inactivate mitotic functions to allow the metaphase/anaphase transition and exit from mitosis; this too could occur by promoting loss of mitotic cyclin protein.
To identify the morula gene, we have isolated a 40 kb region on 2R by deficiency mapping that contains the gene. Transformation rescue experiments combined with sequencing of morula alleles are being used to test candidate genes in this region for morula function. Identification of the morula gene product will provide insight into a cell cycle regulator that serves a dual funciton in promoting exit from mitosis and maintaining absence of mitosis during the endo cycle.