Regulation of cell growth and proliferation of neural progenitor cells in the central brain of Drosophila melanogaster by protein kinase Mbt and the nucleolar protein Mbm.
Developmental Biology
Evolutionary Cell and Developmental Biology (Zoology)
Final Report Abstract
The major objective of this application was to study cell intrinsic mechanisms regulating proliferation of neuroblasts as the progenitor cells of the developing Drosophila central nervous system. Based on the funding decision, we continued work on a previously characterized mutant, mushroom body miniature (mbm), which impairs NB proliferation. We substantiated the finding that Mbm is required for ribosomal biogenesis most likely at the level of pre-rRNA processing. Yet the molecular mechanisms still remain elusive. Furthermore, Mbm function is potentially regulated by arginine methylation. Our results also support the concept of stem (progenitor) cell specific mechanisms of ribosome biogenesis. In the second project part, we characterized two other structural brain mutants, small mushroom bodies (smu) and mushroom bodies reduced (mbr) at the molecular and phenotypic level. Again, the identified gene products encode for proteins required in general cellular processes (replication and cell cycle control). We attribute the particular sensitivity of mushroom body development to the hypomorphic nature of these mutations and the usual proliferation capacity of mushroom body neuroblasts. Finally, we have used a brain tumor model to identify a candidate modulator. Knock-down of this gene greatly reduced tumor growth. Although this finding needs further investigation, we consider this project as most promising for future translational research.
Publications
- (2015) snoRNAs are a novel class of biologically relevant Myc targets. BMC Biol. 13(1):25
Herter, E.K., Strauch, M., Gallant, M., Wolf, E., Raabe, T., Gallant, P.
(See online at https://doi.org/10.1186/s12915-015-0132-6) - (2016) Mcm3 replicative helicase mutation impairs neuroblast proliferation and memory in Drosophila. Genes, Brain & Behav. 15, 647-659
Blumröder, R., Glunz, A., Dunkelberger, B.S., Serway, C.N., Berger, C., Mentzel, B., de Belle, J.S., Raabe, T.
(See online at https://doi.org/10.1111/gbb.12304)
