A crucial yet poorly understood step in neural circuit formation is the development of synaptogenic competence, the ability of neurons to form synapses. The rate at which synaptogenic competence develops is species-specific, developing in a matter of days in mouse neurons compared to many months in human neurons. This step requires a transition in a neuron’s molecular program from axon growth and pathfinding to cell-cell contact formation and synaptic differentiation. The mechanisms controlling this transition are largely unknown.
Whether axon guidance and synaptogenesis require entirely different molecular mechanisms, or whether the same molecules are simply re-used and have context-dependent functions is still largely unclear. The evidence to date suggests that axon guidance molecules, such as the Semaphorins and their Neuropilin/Plexin receptors, continue to be expressed throughout adulthood. Synaptogenic adhesion molecules, such as Neurexins and Neuroligins, on the other hand appear to function exclusively in synaptogenesis.
This project will examine the molecular mechanisms that control the switch in developmental program from axon guidance to synaptogenesis using automated imaging screening of cell cultures, transcriptome analysis of developing mouse and human neurons, and in vivo analysis of candidate molecules in mouse models.
This is a collaborative project between the labs of Pierre Vanderhaeghen (Stem Cell and Developmental Neurobiology Lab), Joris de Wit (Laboratory of Synapse Biology) at the VIB-KU Leuven Center for Brain & Disease Research, Belgium, and Franck Polleux (visiting professor at the VIB-KU Leuven Center for Brain & Disease Research and Professor in the Department of Neuroscience of Columbia University-USA).
The candidate will be based at the VIB-KU Leuven Center for Brain & Disease Research.
This project focuses on investigating the mechanisms determining synaptogenic competence in mouse and human neurons.
You will make use of mouse and human neuronal cell cultures, automated high-content imaging and advanced image analysis, transcriptome and proteome analysis, to identify candidate genes regulating synapse formation in mouse and human cortical pyramidal neurons.
The role of identified candidate genes will subsequently be tested in vivo, using mouse genetics, xenotransplantation models, viral vector approaches, in combination with (ultra)structural and functional analysis of synaptic connectivity.
We are seeking a highly motivated, independent, enthusiastic, critical and creative individual to join our teams. The candidate should have a strong interest in synapse biology and developmental neurobiology.