Genetic mechanisms that regulate left/right asymmetric neuron size

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DESCRIPTION (provided by applicant): PROJECT SUMMARY "Genetic and functional analysis of left/right asymmetric neuron size" Nervous systems are generally bilaterally symmetric on a structural level but are strongly lateralized (left/right asymmetric) on a functional level. Molecular and morphological correlates of functional laterality are sparse and, therefore, functional lateralization is poorly understood. However, it has been noted that symmetrically positioned, bilateral groups of neurons in functionally lateralized brain regions differ in the size of their soma. The genetic mechanisms that program these left/right asymmetric soma size differences are unknown. In fact, it is generally not well understood how the soma size of neurons is controlled throughout the nervous system (which contains neurons that differ in size by several orders of magnitude). We propose here to utilize the nematode C.elegans to study how the size difference of two, otherwise bilaterally symmetric chemosensory neuron is genetically controlled. To identify genes, we visualize the size difference in the neuron pair in a large panel of different genetic mutant backgrounds, which affect previously known pathways that control cell size in other systems. We will examine where these presumptive size regulators are expressed and how their expression is regulated. We will test whether altering the size of the two neurons impacts on specific response parameters to sensory cues. In sum, we combine two exciting and actively pursued areas of research that have not been combined before - the study of left/right asymmetry in the nervous system and the study of size control, using a model system that is particularly amenable to study these problems. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE "Genetic and functional analysis of left/right asymmetric neuron size" This grant proposal sets out to begin an analysis of the genetic regulation and functional relevance of cell size differences in the nervous system, using the nematode C.elegans as a model system. Lateral differences in neuron cell size are conserved across phylogeny, can be observed in humans and are disrupted in psychiatric disorders, illustrating the overall importance of this study.