Regulation von Zellwachstum und Proliferation von neuralen Vorläuferzellen im Zentralhirn von Drosophila melanogaster durch die Proteinkinase Mbt und das nukleoläre Protein Mbm.
Entwicklungsbiologie
Evolutionäre Zell- und Entwicklungsbiologie der Tiere
Zusammenfassung der Projektergebnisse
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.
Projektbezogene Publikationen (Auswahl)
- (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.
(Siehe online unter 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.
(Siehe online unter https://doi.org/10.1111/gbb.12304)
