Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
Neural Dev. 2009 Dec 11;4:44. doi: 10.1186/1749-8104-4-44.
Specific dorsomedial (DM) neuroblast lineages of the Drosophila brain amplify their proliferation through generation of transit amplifying intermediate progenitor cells. Together, these DM neuroblast lineages comprise over 5,000 adult-specific neural cells and thus represent a substantial part of the brain. However, no information is currently available about the structure or function of any of the neural cells in these DM lineages. In this report we use MARCM-based clonal analysis together with immunocytochemical labeling techniques to investigate the type and fate of neural cells generated in the DM lineages.
Genetic cell lineage-tracing and immunocytochemical marker analysis reveal that DM neuroblasts are multipotent progenitors that produce a set of postembryonic brain glia as well as a large number of adult-specific protocerebral neurons. During larval development the adult-specific neurons of each DM lineage form several spatially separated axonal fascicles, some of which project along larval brain commissural structures that are primordia of midline neuropile. By taking advantage of a specific Gal4 reporter line, the DM-derived neuronal cells can be identified and followed into early pupal stages. During pupal development the neurons of the DM lineages arborize in many parts of the brain and contribute to neuropile substructures of the developing central complex, such as the fan-shaped body, noduli and protocerebral bridge.
Our findings provide cellular and molecular evidence for the fact that DM neuroblasts are multipotent progenitors; thus, they represent the first identified progenitor cells in the fly brain that have neuroglioblast functions during postembryonic development. Moreover, our results demonstrate that the adult-specific neurons of the DM lineages arborize widely in the brain and also make a major contribution to the developing central complex. These findings suggest that the amplification of proliferation that characterizes DM lineages may be an important requirement for generating the large number of neurons required in highly complex neuropile structures such as the central complex in the Drosophila brain.
果蝇大脑特定的背内侧（DM）神经母细胞通过产生过渡扩增中间祖细胞来扩增其增殖。这些 DM 神经母细胞谱系共同构成了超过 5000 个成虫特异性神经细胞，因此代表了大脑的重要组成部分。然而，目前尚无关于这些 DM 谱系中任何神经细胞的结构或功能的信息。在本报告中，我们使用基于 MARCM 的克隆分析以及免疫细胞化学标记技术来研究 DM 谱系中产生的神经细胞的类型和命运。
遗传细胞谱系追踪和免疫细胞化学标记分析表明，DM 神经母细胞是多能祖细胞，可产生一组胚胎后大脑神经胶质以及大量成虫特异性原脑神经元。在幼虫发育过程中，每个 DM 谱系的成虫特异性神经元形成几个空间上分离的轴突束，其中一些沿着幼虫脑连合结构投射，这些结构是中线神经叶的原基。利用特定的 Gal4 报告基因系，可以鉴定和跟踪 DM 衍生的神经元细胞进入早期蛹期。在蛹发育过程中，DM 谱系的神经元在大脑的许多部位分枝，并为正在发育的中枢复合体的神经叶亚结构做出贡献，例如扇形体、小结和原脑桥。
我们的研究结果为 DM 神经母细胞是多能祖细胞这一事实提供了细胞和分子证据；因此，它们代表了在果蝇大脑中首次鉴定的具有神经胶质母细胞功能的祖细胞，在胚胎后发育过程中。此外，我们的研究结果表明，DM 谱系的成虫特异性神经元在大脑中广泛分枝，并对正在发育的中枢复合体做出重大贡献。这些发现表明，DM 谱系中增殖的扩增可能是产生大量神经元的重要要求，这些神经元是果蝇大脑中高度复杂的神经叶结构（如中枢复合体）所必需的。
