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The p21-activated kinase Mbt is a component of the apical protein complex in central brain neuroblasts and controls
Juliane Melzer1, Karoline F Kraft, Rolf Urbach
1Universität Würzburg, Institut für Medizinische Strahlenkunde und Zellforschung, Versbacherstrasse 5, Würzburg, Germany.
Abstract:
The final size of the central nervous system is determined by precisely controlled generation, proliferation and death of neural stem cells. We show here that the Drosophila PAK protein Mushroom bodies tiny (Mbt) is expressed in central brain progenitor cells (neuroblasts) and becomes enriched to the apical cortex of neuroblasts in a cell cycle- and Cdc42-dependent manner. Using mushroom body neuroblasts as a model system, we demonstrate that in the absence of Mbt function, neuroblasts and their progeny are correctly specified and are able to generate different neuron subclasses as in the wild type, but are impaired in their proliferation activity throughout development. In general, loss of Mbt function does not interfere with establishment or maintenance of cell polarity, orientation of the mitotic spindle and organization of the actin or tubulin cytoskeleton in central brain neuroblasts. However, we show that mbt mutant neuroblasts are significantly reduced in cell size during different stages of development, which is most pronounced for mushroom body neuroblasts. This phenotype correlates with reduced mitotic activity throughout development. Additionally, postembryonic neuroblasts are lost prematurely owing to apoptosis. Yet, preventing apoptosis did not rescue the loss of neurons seen in the adult mushroom body of mbt mutants. From these results, we conclude that Mbt is part of a regulatory network that is required for neuroblast growth and thereby allows proper proliferation of neuroblasts throughout development.
Insights
The Drosophila PAK protein Mushroom bodies tiny (Mbt) is crucial for neuroblast growth. Loss of Mbt impairs neuroblast proliferation and cell size, impacting central nervous system development.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Neural stem cell proliferation and death are critical for central nervous system development.
- The PAK protein Mushroom bodies tiny (Mbt) is involved in cell cycle regulation.
Purpose of the Study:
- To investigate the role of Mbt in Drosophila neuroblast proliferation and development.
- To understand the molecular mechanisms underlying Mbt's function in neural stem cells.
Main Methods:
- Utilized Drosophila mushroom body neuroblasts as a model system.
- Analyzed Mbt expression patterns in relation to cell cycle and Cdc42.
- Assessed neuroblast proliferation, cell size, polarity, and apoptosis in mbt mutants.
Main Results:
- Mbt is enriched in neuroblast apical cortices in a cell cycle- and Cdc42-dependent manner.
- Loss of Mbt function leads to reduced neuroblast cell size and impaired proliferation.
- Mbt mutants exhibit premature neuroblast loss via apoptosis, but preventing apoptosis does not rescue neuron loss.
Conclusions:
- Mbt is essential for neuroblast growth, which is critical for proper proliferation during development.
- Mbt functions within a regulatory network controlling neuroblast size and mitotic activity.
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