Simeone Antonio, Puelles Eduardo, Acampora Dario, Omodei Daniela, Mancuso Pietro, Giovanni Di Giovannantonio Luca
CEINGE Biotecnologie Avanzate and SEMM European School of Molecular Medicine, via Comunale Margherita 482, 80145 Naples, Italy.
Adv Exp Med Biol. 2009;651:36-46. doi: 10.1007/978-1-4419-0322-8_3.
The mesencephalic dopaminergic (mesDA) neurons play a relevant role in the control of movement, behaviour and cognition. Indeed loss and/or abnormal development of mesDA neurons is responsible for Parkinson's disease as well as for addictive and psychiatric disorders. A wealth of information has been provided on gene functions involved in the molecular mechanism controlling identity, fate and survival of mesDA neurons. Collectively, these studies are contributing to a growing knowledge of the genetic networks required for proper mesDA development, thus disclosing new perspectives for therapeutic approaches of mesDA disorders. Here we will focus on the control exerted by Otx genes in early decisions regulating the differentiation of progenitors located in the ventral midbrain. In this context, the regulatory network involving Otx functional interactions with signalling molecules and transcription factors required to promote or prevent the development of mesDA neurons will be analyzed in detail.
中脑多巴胺能(mesDA)神经元在运动、行为和认知控制中发挥着重要作用。事实上,mesDA神经元的丧失和/或异常发育是帕金森病以及成瘾和精神疾病的病因。关于参与控制mesDA神经元身份、命运和存活的分子机制的基因功能,已经提供了大量信息。总体而言,这些研究有助于人们越来越了解mesDA正常发育所需的遗传网络,从而为mesDA疾病的治疗方法揭示新的前景。在这里,我们将重点关注Otx基因在调节位于腹侧中脑的祖细胞分化的早期决定中所发挥的控制作用。在这种情况下,将详细分析涉及Otx与促进或阻止mesDA神经元发育所需的信号分子和转录因子的功能相互作用的调控网络。