This grant would support the establishment of a dynamic research group in the field of molecular neurobiology at the Karolinska Institute in Stockholm. The PI is a Portuguese national with a PhD from the University of London, and is currently a junior team leader at the Charité Medical University, Berlin.
The group analyses the molecular regulation of neuronal dendritic tree formation during early development of the mouse neocortex. The neocortex is the region of the brain required for complex tasks such as thought and decision-making. Neocortical neurons have highly elaborate branched dendritic trees containing small protrusions called spines that are the main site of information input to the neuron. Defects in the formation of the dendritic tree are at the base of most viable neurodevelopmental disorders, including mental retardation and autism spectrum disorders (ASDs). Unfortunately, very little is known about the molecular mechanisms that regulate formation of the dendritic tree during normal or abnormal development.
The aim of this project is to analyze the role of new players we recently identified, in promoting dendritic tree branching and spine formation in the mammalian neocortex. In particular, we will analyse novel roles of NOMA-GAP, a protein that triggers neocortical dendritic development (Rosario et al. Genes Dev 2012), and newly identified binding partners in directing these processes during brain development. Our approach combines the use of transgenic mouse models, primary neuronal cultures and in vivo manipulation of signalling pathways in the mouse by in utero electroporation, as well as analysis of mouse behaviour. This powerful combination of techniques will allow us to identify novel signalling pathways involved in brain development and to link these not only to the regulation of cellular and cerebral function but also to disease-associated changes in animal behaviour, thereby providing a unifying picture of how disorders such as ASDs arise
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