Mutations in spalt cause a severe but reversible neurodegenerative phenotype in the embryonic central nervous system of Drosophila melanogaster
Mutations in spalt cause a severe but reversible neurodegenerative phenotype in the embryonic central nervous system of Drosophila melanogaster
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DOI：
10.1242/dev.00158
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发表时间：
2002-12-01
期刊：
影响因子：
4.6
通讯作者：
Technau, GM
中科院分区：
文献类型：
--
作者：
Cantera, R;Lüer, K;Technau, GM
spalt基因在黑腹果蝇胚胎中枢神经系统中表达，但其在该组织中的功能尚不清楚。为了研究这个问题，我们使用了多种技术来分析spalt突变胚胎。电镜显示，在没有Spalt的情况下，在胚胎发育的60%，中枢神经系统细胞被由膜质物质填充的扩大的细胞外空间分开。令人惊讶的是，稍微老一点的胚胎（发育的80%）的中枢神经系统表现出几乎野生型的形态。激光共聚焦显微镜的广泛调查显示，spalt突变型中枢神经系统具有异常水平的特定细胞粘附和细胞骨架蛋白。体外神经元分化的延时分析、谱系分析和移植实验证实，该突变导致细胞骨架和粘附缺陷。这些数据表明，在中枢神经系统中，spalt在一个调控通路内运作，影响-catenin Armadillo、其配体N-Cadherin、Notch以及细胞粘附分子Neuroglian、Fasciclin 2和Fasciclin 3的表达。对这些基因表达的影响是持久的，但表型的许多形态学方面是短暂的，导致中枢神经系统稳定组织的顺序冗余概念。
The gene spalt is expressed in the embryonic central nervous system of Drosophila melanogaster but its function in this tissue is still unknown. To investigate this question, we used a combination of techniques to analyse spalt mutant embryos. Electron microscopy showed that in the absence of Spalt, the central nervous system cells are separated by enlarged extracellular spaces populated by membranous material at 60% of embryonic development. Surprisingly, the central nervous system from slightly older embryos (80% of development) exhibited almost wild-type morphology. An extensive survey by laser confocal microscopy revealed that the spalt mutant central nervous system has abnormal levels of particular cell adhesion and cytoskeletal proteins. Time-lapse analysis of neuronal differentiation in vitro, lineage analysis and transplantation experiments confirmed that the mutation causes cytoskeletal and adhesion defects. The data indicate that in the central nervous system, spalt operates within a regulatory pathway which influences the expression of the beta-catenin Armadillo, its ligand N-Cadherin, Notch, and the cell adhesion molecules Neuroglian, Fasciclin 2 and Fasciclin 3. Effects on the expression of these genes are persistent but many morphological aspects of the phenotype are transient, leading to the concept of sequential redundancy for stable organisation of the central nervous system.