Otx2 expression is restricted to dopaminergic neurons of the ventral tegmental area in the adult brain
Otx2 expression is restricted to dopaminergic neurons of the ventral tegmental area in the adult brain
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DOI：
10.1387/ijdb.092974ms
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发表时间：
2010-01-01
影响因子：
0.7
通讯作者：
Simeone, Antonio
中科院分区：
文献类型：
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作者：
Di Salvio, Michela;Di Giovannantonio, Luca G.;Simeone, Antonio
中脑-间脑多巴胺能 (mdDA) 神经元控制运动、感觉运动和动机行为，它们的退化或功能异常与重要的病理学相关，例如帕金森病和精神疾病。尽管付出了巨大的努力，但对黑质 (SN) 和腹侧被盖区 (VTA) mdDA 神经元的身份、生存和神经变性易感性的差异控制的分子基础和遗传因素仍知之甚少。我们之前已经证明转录因子 Otx2 是中脑 DA (mesDA) 祖细胞的身份、命运和增殖所必需的。通过使用小鼠模型和免疫组织化学，我们研究了 Otx2 是否也在有丝分裂后 mdDA 神经元中表达。我们的数据显示，Otx2 在妊娠中后期和成人大脑的有丝分裂后 mesDA 神经元中表达。值得注意的是，Otx2 表达被严格排除在 SN 的 mdDA 神经元之外，并且仅限于 VTA 神经元的相关部分。 Otx2(+)-TH+ 神经元集中于 VTA 的腹侧部分。与其他区域化 VTA 标志物的联合表达表明，Otx2+-TH+ 神经元主要是 Girk2(-) 和 Calb(+)，其中位于 VTA 内侧和最腹侧部分的神经元也是 Ahd2(+)。这些发现表明，Otx2 是第一个在 mdDA 神经发生中被证明具有作用的转录因子，其表达可区分 SN 和相关比例的 VTA 神经元。这支持了 Otx2 可能作为有丝分裂后选择器控制成人 VTA 神经元相关部分的功能特征（例如身份和/或存活）的可能性。
Mesencephalic-diencephalic dopaminergic (mdDA) neurons control motor, sensorimotor and motivated behaviour and their degeneration or abnormal functioning is associated with important pathologies, such as Parkinson's disease and psychiatric disorders. Despite great efforts, the molecular basis and the genetic factors differentially controlling identity, survival and vulnerability to neurodegeneration of mdDA neurons of the substantia nigra (SN) and ventral tegmental area (VTA) are poorly understood. We have previously shown that the transcription factor Otx2 is required for identity, fate and proliferation of mesencephalic DA (mesDA) progenitors. By using mouse models and immunohistochemistry, we have investigated whether Otx2 is expressed also in post-mitotic mdDA neurons. Our data reveal that Otx2 is expressed in post-mitotic mesDA neurons during mid-late gestation and in the adult brain. Remarkably, Otx2 expression is sharply excluded from mdDA neurons of the SN and is restricted to a relevant fraction of VTA neurons. Otx2(+)-TH+ neurons are concentrated to the ventral part of the VTA. Combined expression with other regionalized VTA markers shows that Otx2+-TH+ neurons are prevalently Girk2(-) and Calb(+) and among these, those located in the medial and ventralmost portion of the VTA are also Ahd2(+). These findings indicate that Otx2 represents the first transcription factor with a proven role in mdDA neurogenesis whose expression discriminates between SN and a relevant proportion of VTA neurons. This supports the possibility that Otx2 may act as a post-mitotic selector controlling functional features (e.g. identity and/or survival) of a relevant fraction of VTA neurons in the adult.