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Project

Impact of human-specific gene duplications on the development of cerebral cortex

The cerebral cortex is a highly complex structure that has undergone considerable expansion and complexification during recent hominid evolution. Recently, the group of Professor Vanderhaeghen discovered several dozens of hominid-specific (HS) gene duplications that are dynamically expressed during human corticogenesis. The function of most of these genes is currently still unknown, but could be involved in several species-specific mechanisms of cortical neuron generation and differentiation. Human neurons present specific features regarding morphology, such as more complex and longer dendrites and a higher density of dendritic spines. Also and most strikingly, human neurons of specific cortical areas develop along a protracted period (up to years in the prefrontal cortex), which is thought to underlie some of the human-specific properties of our brain. My project will focus on several of HS genes, including RASA4CP, isoforms of PDE4DIP, NPIPA5 and GOLGA8A, to determine whether and how they are involved in neurodevelopment, and then explore their potential function during neurodevelopment. We selected these genes on the basis of their dynamic expression during human corticogenesis and their upregulation during cortical neuron differentiation. On the one hand we will screen HS genes using gain of function in the mouse embryonic cortex using in utero electroporation, by examining the potential impact of these genes on neuronal generation, migration and morphogenesis. On the other hand, using unique models of human corticogenesis pioneered in the lab, we will test the impact of promising genes in human cortical cells, both in vitro and following xenotransplantation in the mouse to follow their latest steps of development. This combined approach, which was already successful in the lab to reveal the newly discovered HS gene family Notch2NL should enable to identify which and how HS genes can act as species-specific modifiers of cortical development.

Date:7 Jan 2019 →  31 Mar 2022
Keywords:LRRC37B, FRMPD2B, Gene duplication, Evolution, Neurodevelopment, Corticogenesis, RASA4CP, PDE4DIP, GOLGA8A, NPIPA5
Disciplines:Evolutionary developmental biology, Developmental genetics, Developmental biology, Developmental neuroscience
Project type:PhD project