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.

• Applicant: Professor Dr. Thomas Raabe
• Subject Area: Developmental Neurobiology ; Developmental Biology ; Evolutionary Cell and Developmental Biology (Zoology)
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 264042185

Neuroblasts, the neural progenitor cells of the developing Drosophila central nervous system, have emerged as key model system for many aspects of stem cell biology such as specification of distinct progenitor subtypes, their lineage analysis and the identification of extrinsic and intrinsic factors, which influence neuroblast proliferation. Proliferation of neuroblasts during development is strictly controlled by subtype-specific proliferation and quiescence phases and by temporal patterning mechanisms to sequentially generate the right number of different neuron types. Neuroblast proliferation is also influenced by systemic factors and local signals to finally ensure coordinated development of the whole organism. Yet, also cell intrinsic information must be integrated, which allow for proper neuroblast growth as a prerequisite for continuous proliferation. Recently, we have characterized two mutants, mushroom bodies tiny (mbt) and mushroom body miniature (mbm), which do not affect the general brain organization but instead reduce the overall brain size, which is most evident for the mushroom bodies. Mbm and mbt neuroblasts divide in a normal asymmetric manner but are impaired in their proliferative capacity, which correlates with a decrease in cell size. In the case of the cortical localized protein kinase Mbt, the major objective will be to identify upstream regulators and downstream effectors in neuroblasts with a major emphasis on RhoGTPase dependent signaling processes and integration into systemic growth control signals. In the case of Mbm, we want to clarify its nucleolar function in ribosome biogenesis. The transcriptional regulation of the mbm by Myc and the phosphorylation of Mbm by protein kinase CK2 implicate Mbm as integration point of systemic and cell intrinsic growth signals, which will be tested by genetic and biochemical experiments.

• DFG Programme: Research Grants