From 3D surface models to the cellular and molecular architecture of the dentate nucleus: characterizing human-typical traits in the cerebellum

与大多数哺乳动物相比，灵长类动物的小脑半球体积更大，猿类和人类的小脑半球体积更大。灵长类齿状动物长期以来根据齿状形态划分为较老的背侧小回体和较新的腹侧大回体，最近这一划分与小脑到前额叶皮层的主要投射的出现有关，因此也与相关的前额叶特定人类能力的发展有关（例如执行功能）。我们最近使用详细的3D表面模型对人类齿状体形态进行了重新检查，结果表明，核的主要部分与齿状体的系统发育上较古老的微回背侧运动部分更为相关，人类齿状体的特征是其折叠和表面增加，而不是腹侧大回区的出现。在这项提议中，我们希望进一步研究其他类人猿的齿状体，并研究齿状体折叠的机制。本研究计划的第一个目标（Aim 1）是确定人类齿状齿与猿和灵长类齿状齿之间的同源性，以便在系统发育上准确地重建新获得特征的外观，即人类特异性特征。本提案的第二个目标（目标2）是将齿状体的显著折叠与潜在的细胞和分子过程联系起来，以便更好地理解猿和人类齿状体中褶皱出现的机制。我们希望了解这些遗传/分子机制将使我们能够更好地重建类人猿的进化，此外，我们希望从长远来看，将齿状类人猿的适应与人类神经系统疾病（如弗里德赖希共济失调和特发性震颤）联系起来。

Compared to most mammals the cerebellar hemispheres are expanded in size in primates and even more so in apes and humans. A long-standing division of the primate dentate into an evolutionary older dorsal microgyric and a newer ventral macrogyric half based on dentate morphology has recently been linked to the emergence of a major projection from the cerebellum to the prefrontal cortex, and hence also to the development of related prefrontal specific human abilities (e.g. executive functions). Our recent re-examination of the human dentate morphology using detailed 3D surface models shows that the major part of the nucleus is much more related to the phylogenetically older microgyric dorsal motor part of the dentate and that the characteristic of the human dentate is its folding and surface increase and not the emergence of a ventral macrogyric region. In this proposal we want to further study the dentate in other hominoids and also to study the mechanisms that underlie dentate folding. The first goal (Aim 1) of this research proposal is to identify homologies between the human dentate and the dentate of apes and primates in order to phylogenetically accurately reconstruct the appearance of newly acquired features, i.e., human specific traits. The second goal (Aim 2) of this proposal is to relate the remarkable folding of the dentate to underlying cellular and molecular processes in order to better understand the mechanisms that underlie the emergence of folds in the ape and human dentate. We hope that understanding these genetic/molecular mechanisms will allow us to better reconstruct hominoid evolution and in addition we hope in the long run to relate dentate hominoid adaptations to human neurological disease such as Friedreich's ataxia and essential tremor.