Blaess Sandra, Ang Siew-Lan
Institute of Reconstructive Neurobiology, Life and Brain Center, University of Bonn, Bonn, Germany.
Wiley Interdiscip Rev Dev Biol. 2015 Mar-Apr;4(2):113-34. doi: 10.1002/wdev.169. Epub 2015 Jan 6.
Midbrain dopaminergic neurons are involved in regulating motor control, reward behavior, and cognition. Degeneration or dysfunction of midbrain dopaminergic neurons is implicated in several neuropsychiatric disorders such as Parkinson's disease, substance use disorders, depression, and schizophrenia. Understanding the developmental processes that generate midbrain dopaminergic neurons will facilitate the generation of dopaminergic neurons from stem cells for cell replacement therapies to substitute degenerating cells in Parkinson's disease patients and will forward our understanding on how functional diversity of dopaminergic neurons in the adult brain is established. Midbrain dopaminergic neurons develop in a multistep process. Following the induction of the ventral midbrain, a distinct dopaminergic progenitor domain is specified and dopaminergic progenitors undergo proliferation, neurogenesis, and differentiation. Subsequently, midbrain dopaminergic neurons acquire a mature dopaminergic phenotype, migrate to their final position and establish projections and connections to their forebrain targets. This review will discuss insights gained on the signaling network of secreted molecules, cell surface receptors, and transcription factors that regulate specification and differentiation of midbrain dopaminergic progenitors and neurons, from the induction of the ventral midbrain to the migration of dopaminergic neurons. For further resources related to this article, please visit the WIREs website.
The authors have declared no conflicts of interest for this article.
中脑多巴胺能神经元参与调节运动控制、奖赏行为和认知。中脑多巴胺能神经元的退化或功能障碍与多种神经精神疾病有关，如帕金森病、物质使用障碍、抑郁症和精神分裂症。了解产生中脑多巴胺能神经元的发育过程，将有助于从干细胞中生成多巴胺能神经元，用于细胞替代疗法，以替代帕金森病患者中退化的细胞，并将推动我们对成人大脑中多巴胺能神经元功能多样性如何建立的理解。中脑多巴胺能神经元的发育是一个多步骤过程。在腹侧中脑诱导之后，一个独特的多巴胺能祖细胞区域被确定，多巴胺能祖细胞经历增殖、神经发生和分化。随后，中脑多巴胺能神经元获得成熟的多巴胺能表型，迁移到它们的最终位置，并建立与前脑靶标的投射和连接。本综述将讨论从腹侧中脑诱导到多巴胺能神经元迁移过程中，在调节中脑多巴胺能祖细胞和神经元的特化与分化的分泌分子、细胞表面受体和转录因子的信号网络方面所获得的见解。有关本文的更多资源，请访问WIREs网站。
作者声明本文不存在利益冲突。
