Molecular Mechanisms of Visual Thalamic Development

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DESCRIPTION (provided by applicant): How brain regions form and establish appropriate connections has critical implications for our understanding of developmental neurologic disorders. A mouse model in which visual sensory axons are re-routed to the auditory region of the thalamus after surgical deafferentation enables us to study potential axon guidance cues to the diencephalon. While axon guidance at the optic disk, tract and tectum has been well studied, little is known about mechanisms mediating ingrowth to thalamus. I will use gene microarrays to identify candidate guidance molecules from differential expression patterns between the visual and auditory thalamus in normal and rewired mice. Two novel candidates, the Zic1 and Zic4 transcription factors, exhibit selective expression within the visual thalamus and potentially regulate the expression of soluble guidance cues, including En-2. I will test whether Zic1 and Zic4 expression is necessary and sufficient for axon targeting using in vitro and in vivo assays. Elucidating the process by which regions of the thalamus acquire normal and novel inputs will inform our mechanistic models of disease involving aberrant pathway formation as well as the potential for plasticity in neural connections after stroke or injury.