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Genetic links between development and evolution of the human cerebral cortex

Objective

"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."

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /natural sciences/biological sciences/evolutionary biology
  • /natural sciences/biological sciences/neurobiology

Call for proposal

ERC-2013-ADG
See other projects for this call

Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

UNIVERSITE LIBRE DE BRUXELLES
Address
Avenue Franklin Roosevelt 50
1050 Bruxelles
Belgium
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 473 937
Principal investigator
Pierre Vanderhaeghen (Prof.)
Administrative Contact
Anastasios Perimenis (Mr.)

Beneficiaries (1)

UNIVERSITE LIBRE DE BRUXELLES
Belgium
EU contribution
€ 2 473 937
Address
Avenue Franklin Roosevelt 50
1050 Bruxelles
Activity type
Higher or Secondary Education Establishments
Principal investigator
Pierre Vanderhaeghen (Prof.)
Administrative Contact
Anastasios Perimenis (Mr.)