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Regulation der Zahl und des Proliferationsverhaltens von neuralen Stammzellen während der Entwicklung des ZNS von Drosophila

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Neuroblasts, the neural progenitor cells of the 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 identfication of extrinsic and instrinsic factors which control proliferation and cell division. During development, distinct neuroblasts not only show an intricate balance between quiescence and proliferation phases but they also differ in their rate and duration of proliferation. Neuroblast proliferation is coordinated with developmental timing by systemic factors and local signals. Yet, also cell intrinsic mechanisms must exist, which allow for proper neuroblast growth as a prerequisite for continous proliferation. Recently, we have characterized two mutations, mushroom bodies tiny (mbt) and mushroom body miniature (mbm), which do not affect the overall brain anatomy but instead affect brain size, most prominently the mushroom bodies, a paired neuropil structure involved in learning and meory processes. Phenotypic analysis of mbm and mbt neuroblasts revelaed a significant decrease in cell size. Taking advantage of the complete description of the lineages of the four mushroom body neuroblasts, we could show that in mbt, neuroblasts become correctly specified during embryogenesis and divide in a normal asymmetric manner but they proliferate at reduced rates during development and finally die prematurely by apoptosis. Although Mbt function is required in neuroblasts at the cell cortex, the integration of this protein kinase into signaling processes controlling cell growth remains elusive so far. In the case of Mbm we could show that it is a novel component of the nucleolus, which is required for ribosomal biogenesis providing a good explanation for the impaired cell growth. Despite these findings, the molecular function of Mbm is not known.


Laufzeit: von 03.2007 bis 07.2012

DFG ( Sachmittelbeihilfe ) ,Genehmigungsdatum: 14.2.2007