Left/right asymmetric neuronal cell fate specification

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DESCRIPTION (provided by applicant): Nervous system laterality represents one of the most fundamental, yet also least studied phenomena in developmental neurobiology. Nervous systems are generally bilaterally symmetric on an architectural level, yet display significant degrees of functional left/right (L/R) asymmetry. How the left and right side of a brain are made to become different from one another is mechanistically not understood. We propose here to study one of the examples of neuronal laterality in the nematode C.elegans, a system particularly well amenable to study this problem since neuronal laterality can be observed on a single cell level and can be genetically dissected using mutant screening approaches. We will genetically analyze the L/R differential execution of two neuronal specification programs that derive from two bilaterally symmetric blast cells, ABp1papp and ABprpapp. Each blast cell divides several times to produce a distinct set of unpaired, unilateral neurons. We will isolate mutants in which these L/R asymmetric differentiation programs are disrupted. These studies may reveal fundamental principles of neuronal development and may shed light onto the elusive mechanisms of generating L/R asymmetry in the nervous system.