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Molecular mechanisms of central nervous system formation

中枢神经系统形成的分子机制

基本信息

批准号：
07458177
负责人：
SAIGO Kaoru
金额：
$ 3.71万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

Main outcomes of this research are summarized as follows. 1) We first isolated and characterized the eagle, encoding a member of the steroid receptor superfamily in Drosophila. ln the central nervous system, eagle RNA was expressed in a 1imited number of cells, Durning stages 10 and 11, eagle RNA expression was observed in four neuroblasts, NB2-4, NB3-3, NB6-4 and NB7-3. Except for NB6-4, eagle RNA expression reached a maximum at the very begining of expression or in the period of neuroblast delamination. Weak eagle RNA expression was also observed in a few putative progeny of NB7-3 during stages, late 11 and 12. All eagle RNA in abdominal segments disappeared at stage 13. Using an eagle-kinesin-lacZ fusion gene as a reporter, the dlvision, migration, and axonogenesis in eagle-positive cells and their derivatives were examined. At stage 14, several tyeps of neural or glial cells were detected which include EG and EW interneurons joining to the anteior and posterior commissures, respect … More ively. Lack of eagle expression caused altered axonogenesis in an appreciable fraction of eagle-Kinesin-LacZ-positive neurons. Some EG cells failed to acquire the neural fate or underwent an extremely delayd differentiation, while EW neurons produced neurites in abnormal directions, suggestng that eagle may Play a critical role in development of the progeny of eagle-positive neroblasts. 2) The hedgehog gene product, secreted from engrailed-expressing neuroectoderm, is required for the formation of post-S1 neuroblasts in rows 2,5 and 6. The hedgehog protein functions not only as a paracrine but also as anautocrine factor and its transient action on the neuroectoderm 1-2 hours (at 18ﾟC)prior to neuroblast delaminationis necessary and sufficient to form normal neuroblasts. In contrast to epidermal development, hedgehog expression required for neuroblast formation is regulated by neither engrailed nor wingless. hedgehog and wingless bestow composite positional cues on the neuroectodermal regions for S2-S4 neuroblasts at virtually the same time and, consequently, post-S1 neuroblasts in different rows can aquire different positional values along the anterior-posterior axis. The average number of proneural cells for each three eagle-positive S4-S5 neuroblasts was found to be 5-9, the same for S1 NBs, As with wingless, huckbein exprssion in putative proneural regions for certain post-S1 neuroblasts is under the control of hedgehog. hedgehog and wingless are involved in separate, paralle l pathways and loss of either is compensated for by the other in NB7-3, formation. NBs 6-4 and 7-3, arising from the engrailed domain, were also found to be specified by the differential expression of two homeobox genes, gooseberry-distal and engrailed. Less

本研究的主要成果总结如下。1)我们首先分离并鉴定了果蝇中编码类固醇受体超家族成员的鹰。在中枢神经系统中，鹰的RNA在数量有限的细胞中表达，在第10和第11期，鹰的RNA在NB2-4、NB3-3、NB6-4和NB7-3四种神经母细胞中表达。除NB6-4外，Eagle的RNA表达在表达开始时或神经母细胞分层时达到最高。在NB7-3的几个可能的后代中，也观察到了弱的鹰RNA表达，在第11和12期。在第13期，腹部节段的鹰RNA全部消失。以鹰-激动素-LacZ融合基因为报告基因，观察了鹰阳性细胞及其衍生细胞的视觉、迁移和轴突发生。在第14阶段，检测到几种类型的神经细胞或神经胶质细胞，其中包括EG和EW中间神经元连接到前连合和后连合，参照…更生动活泼。缺乏Eagle的表达导致相当一部分Eagle-kinesin-LacZ阳性神经元的轴突发生改变。一些EG细胞未能获得神经命运或经历了极度延迟的分化，而EW神经元则产生了方向异常的突起，提示Eagle可能在Eagle阳性神经母细胞后代的发育中发挥关键作用。2)表达的神经外胚层分泌的Hedgehog基因产物是形成S1后第2、5、6行神经母细胞所必需的。Hedgehog蛋白不仅具有旁分泌功能，还具有自分泌因子的功能，其在神经母细胞分层前1-2小时(18ﾟC)对神经外胚层的瞬时作用是形成正常神经母细胞的必要条件和充分条件。与表皮发育相反，神经母细胞形成所需的刺猬表达既不受有翼的也不受无翼的调节。刺猬和无翼在S2-S4神经母细胞的神经外胚层区域几乎同时给予复合位置线索，因此，不同排的后S1神经母细胞可以获得沿前后轴线的不同位置值。每三个鹰阳性的S4-S5神经母细胞的平均前神经细胞数为5-9个，与S1NBS的相同，因为S1后的某些神经母细胞在推定的前神经区无翼、Huckbein表达是在刺猬的控制下。刺猬和无翼参与了独立的、平行的L路径，在NB7-3编队中，两者的损失由另一个弥补。NBS 6-4和7-3也被发现是由两个同源框基因的差异表达所特有的，这两个基因分别是醋栗远端基因和渐变结构域。较少