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.

蛋白激酶 Mbt 和核仁蛋白 Mbm 对果蝇中枢神经祖细胞生长和增殖的调节。

• 批准号: 264042185
• 负责人: Professor Dr. Thomas Raabe
• 金额: --
• 依托单位: Abteilung Molekulare Genetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/264042185?language=en
• 关键词: Regulation; cell; growth; proliferation; neural

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.

神经母细胞是发育中的果蝇中枢神经系统的神经前体细胞，已成为干细胞生物学许多方面的关键模型系统，如不同前体亚型的指定，其谱系分析和鉴定影响神经母细胞增殖的外在和内在因素。发育过程中神经母细胞的增殖受到亚型特异性增殖和静止期以及时间模式化机制的严格控制，以顺序产生正确数量的不同神经元类型。成神经细胞的增殖也受到全身因素和局部信号的影响，最终保证整个机体的协调发展。然而，还必须整合细胞内在信息，这允许适当的成神经细胞生长作为持续增殖的先决条件。最近，我们发现了两种突变体，微小蘑菇体（mbt）和微小蘑菇体（mbm），它们不会影响大脑的一般组织，但会减少大脑的整体体积，这在蘑菇体中表现得最为明显。Mbm和mbt成神经细胞以正常的不对称方式分裂，但其增殖能力受损，这与细胞大小的减少有关。在皮质定位的蛋白激酶Mbt的情况下，主要的目标将是确定上游调控和下游效应在成神经细胞的主要重点是RhoGT3依赖的信号传导过程和整合到系统的生长控制信号。在Mbm的情况下，我们想澄清其在核糖体生物发生的核仁功能。Myc对mbm的转录调控和蛋白激酶CK 2对Mbm的磷酸化作用表明Mbm是系统性和细胞内在生长信号的整合点，这将通过遗传和生化实验进行验证。