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

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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.