Urbach Rolf, Schnabel Ralf, Technau Gerhard M
Institut für Genetik, Universität Mainz, D-55099 Mainz, Germany.
Development. 2003 Aug;130(16):3589-606. doi: 10.1242/dev.00528.
In the Drosophila embryo, studies on CNS development have so far mainly focused on the relatively simply structured ventral nerve cord. In the trunk, proneural genes become expressed in small cell clusters at specific positions of the ventral neuroectoderm. A lateral inhibition process mediated by the neurogenic genes ensures that only one cell within each proneural cluster delaminates as a neural stem cell (neuroblast). Thus, a fixed number of neuroblasts is formed, according to a stereotypical spatiotemporal and segmentally repeated pattern, each subsequently generating a specific cell lineage. Owing to higher complexity and hidden segmental organisation, the mechanisms underlying the development of the brain are much less understood. In order to pave the way towards gaining deeper insight into these mechanisms, we have undertaken a comprehensive survey of early brain development until embryonic stage 11, when all brain neuroblasts have formed. We describe the complete spatiotemporal pattern of formation of about 100 brain neuroblasts on either side building the trito-, deuto- and protocerebrum. Using 4D-microscopy, we have uncovered various modes of neuroblast formation that are related to specific mitotic domains of the procephalic neuroectoderm. Furthermore, a detailed description is provided of the dynamic expression patterns of proneural genes (achaete, scute, lethal of scute, atonal) in the procephalic neuroectoderm and the individual neuroblasts. Finally, we present direct evidence that, in contrast to the trunk, adjacent cells within specific domains of the procephalic neuroectoderm develop as neuroblasts, indicating that mechanisms controlling neuroblast formation differ between head and trunk.
在果蝇胚胎中，迄今为止对中枢神经系统发育的研究主要集中在结构相对简单的腹侧神经索。在躯干中，原神经基因在腹侧神经外胚层特定位置的小细胞簇中表达。由神经源基因介导的侧向抑制过程确保每个原神经簇中只有一个细胞作为神经干细胞（神经母细胞）脱层。因此，根据一种刻板的时空和节段重复模式，形成了固定数量的神经母细胞，每个神经母细胞随后产生特定的细胞谱系。由于大脑发育的机制具有更高的复杂性和隐藏的节段组织，人们对其了解要少得多。为了深入了解这些机制，我们对胚胎发育到第11阶段（此时所有脑神经元母细胞都已形成）的早期大脑发育进行了全面调查。我们描述了构成后脑、中脑和前脑的两侧约100个脑神经元母细胞形成的完整时空模式。利用四维显微镜，我们发现了与前脑神经外胚层特定有丝分裂域相关的多种神经母细胞形成模式。此外，还详细描述了前脑神经外胚层和单个神经母细胞中原神经基因（achaete、scute、scute致死、无调）的动态表达模式。最后，我们提供了直接证据，与躯干不同，前脑神经外胚层特定区域内的相邻细胞发育为神经母细胞，这表明头部和躯干控制神经母细胞形成的机制不同。
