Molecular mechanisms of central nervous system formation

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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