Roussa Eleni, Krieglstein Kerstin
Department for Neuroanatomy, Center of Anatomy, Georg-August-University Göttingen, 37075 Göttingen, Germany.
Cell Tissue Res. 2004 Oct;318(1):23-33. doi: 10.1007/s00441-004-0916-4. Epub 2004 Aug 19.
Cell-fate decisions along the dorsoventral and anterior-posterior axis of the neural tube are dictated by factors from signaling and organizing centers. According to the prevailing notion, the formation of mesencephalic dopaminergic neurons is directed by diffusable signals from the notochord, floor plate, and isthmic organizer. Sonic hedgehog (Shh), secreted by the notochord and floor plate, and fibroblast growth factor (FGF) 8, secreted by the isthmus, are thought to be key molecules involved in the development of midbrain dopaminergic neurons. During the last decade, the introduction of elegant explant culture systems and the generation of transgenic and mutant mice have greatly contributed to a better understanding of the molecular signals that direct the induction and specification of midbrain dopaminergic neurons. In this context, experimental evidence has challenged the dominant roles of Shh and FGF8 in dopaminergic neuron development. Additional molecules have been identified as being required for the generation of mesencephalic dopaminergic neurons, particularly members of the transforming growth factor beta superfamily.
神经管背腹轴和前后轴上的细胞命运决定由信号传导和组织中心的因子决定。根据普遍观点，中脑多巴胺能神经元的形成由来自脊索、底板和峡部组织者的可扩散信号引导。脊索和底板分泌的音猬因子（Shh）以及峡部分泌的成纤维细胞生长因子（FGF）8被认为是参与中脑多巴胺能神经元发育的关键分子。在过去十年中，精巧的外植体培养系统的引入以及转基因和突变小鼠的产生，极大地促进了人们对指导中脑多巴胺能神经元诱导和特化的分子信号的更好理解。在这种背景下，实验证据对Shh和FGF8在多巴胺能神经元发育中的主导作用提出了挑战。已鉴定出其他分子是中脑多巴胺能神经元生成所必需的，特别是转化生长因子β超家族的成员。
