"The mechanisms underlying the evolution of the human brain constitute one of the most fascinating unresolved questions of biology. The cerebral cortex has evolved rapidly in size and complexity in the hominid lineage, which is likely linked to quantitative and qualitative divergence in patterns of cortical development.
On the other hand, comparative genomics has revealed recently the existence of a number of ""hominid-specific"" genes, which constitute attractive candidates to underlie critical aspects of human brain evolution, but their function remains essentially unexplored, mostly because of the lack of appropriate experimental systems.
Here we propose to test a simple and radical hypothesis: that key species-specific features of the development of the human cerebral cortex, in particular the generation and differentiation of pyramidal neurons, are linked functionally to the emergence of hominid-specific (HS) genes controlling corticogenesis.
To achieve this high risk / high gain goal, we will first determine which HS genes are expressed in the human developing cortex in vivo, using a combination of genome-wide and in situ gene detection analyses, in order to select those most likely to impact corticogenesis.
The function of candidate HS genes will be determined using innovative models of human corticogenesis based on pluripotent stem cells, developed recently in our laboratory, as well as ex vivo cultures of human fetal cortex. In addition, the developmental and evolutionary impact of HS genes will be examined in a non-hominid context, the mouse embryonic cortex.
By identifying the function of hominid-specific genes in cortical developpment, we will uncover specific genetic mechanisms linking functionally the development and evolution of the human brain, with broad implications in neurobiology, developmental and evolutionary biology."
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