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Pyramidal neuron polarity decisions during migration and axonal outgrowth in the developing mammalian cerebral cortex (Neuronal polarity)
Start date: Oct 1, 2008, End date: Sep 30, 2011 PROJECT  FINISHED 

During embryonic brain development, pyramidal projection neurons are born in the ventricular zone and migrate radially towards the upper part of the cortex to form the cortical plate. These neurons also have to develop dendrites and axons in order to make connections. Several brain diseases and mental illness derive from defects in neuronal migration and positioning or in axon-target interactions for the establishment of synaptic circuitry. Studies with cultured pyramidal neurons have shown that similar polarity decisions, and many of the same proteins, specify the direction of migration and the orientation of axon outgrowth. However, in vivo, in developing brain, it appears that axons start growing before the completion of neuronal migration, and the axon is always positioned at the opposite side to the migration front. An important open question is to understand how the neuron is able to distinguish spatially and temporally these two opposite polarity signals by using the same polarity proteins in vivo. The results suggest that the situation in a polarized epithelium in vivo is different to that observed in vitro. Indeed, in non-mammalian organism such as the fly, some polarity proteins seem to be dispensable for polarized neuronal migration. We propose to determine the position of the apical pole of a pyramidal neuron during its migration and differentiation in vivo during mouse brain development. We will identify the timing of possible switches in cell polarity relative to the timing of axon emergence, and identify molecules involved in these decisions. Importantly, our studies will be done in vivo and in a living brain slice culture assay.

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