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

从 3D 表面模型到齿状核的细胞和分子结构：表征小脑中的人类典型特征

基本信息

批准号：
200054879
负责人：
Privatdozent Dr. Fahad Sultan
金额：
--
依托单位：
Institutionen för integrativ medicinsk biologi (IMB)
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2011
资助国家：
德国
起止时间：
2010-12-31 至 2014-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/200054879?language=en
关键词：
3D surface models cellular molecular

项目摘要

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.

与大多数哺乳动物相比，灵长类动物的小脑半球在尺寸上扩大，猿和人类的小脑半球更大。灵长类动物的齿状回根据齿状回的形态分为较老的背侧小回区和较新的腹侧大回区，这一长期存在的划分最近被认为与从小脑到前额叶皮质的主要投射的出现有关，因此也与相关的前额叶特异性人类能力（例如执行功能）的发展有关。我们最近重新检查的人类齿状回形态，使用详细的三维表面模型表明，核的主要部分是更相关的神经遗传老年人的小回背侧运动部分的齿状回和人类齿状回的特点是它的折叠和表面增加，而不是出现的腹侧大回区。在这个提议中，我们想进一步研究其他类人猿的齿状结构，并研究齿状结构折叠的机制。本研究提案的第一个目标（Aim 1）是确定人类齿状突与猿和灵长类齿状突之间的同源性，以便在遗传学上准确地重建新获得特征的外观，即，人类特有的特征该建议的第二个目标（Aim 2）是将齿状突起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突起中出现折叠的机制。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进化，此外，我们希望从长远来看，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齿状类人猿适应。