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Comments on Zhang, Feifan et al. (2009) International Worm Meeting "Automated Screening for Mutants Defective in ASE Asymmetric Neuronal Fate Specification." (0)
Overview
Zhang, Feifan, & Hobert, Oliver (2009). Automated Screening for Mutants Defective in ASE Asymmetric Neuronal Fate Specification presented in International Worm Meeting. Unpublished information; cite only with author permission.
We use an automatic screening method to isolate mutants in which ASE neurons fail in asymmetric cell fate specification. The ASE neurons are a pair of chemosensory neurons that are morphologically symmetric yet functionally asymmetric. The left cell (ASEL) is the primary sodium sensor, while the right cell (ASER) is primarily responsible for potassium and chloride detection. Disruption of this asymmetry results in chemosensory discrimination defects. Previous screens have identified a "bistable feedback loop" that controls the ASEL/R laterality. In order to look for other factors that might be embedded into this complex yet incomplete network, we use the COPAS Biosort system (Union Biometrica, "worm sorter") to automate our screen, which allows us to screen through a large amount of genomes within a much smaller amount of time compared to labor-intensive manual screens. The worm sorter is very powerful in picking up mutants in which the GFP expression varies from that of the wild type population by as little as one single neuron. Using cell-specific GFP reporters, we are able to isolate mutants that have either lost GFP expression in ASEL ("ASEL off") or gained ectopic expression of GFP in ASER ("2 ASEL"). After 8 rounds of four-to-five-hour screen we have identified 21 "ASEL off" mutants from 48,000 genomes and after 15 rounds of similar screen we have isolated 40 "2 ASEL" mutants from 90,000 genomes. Our complementation tests, mapping and characterization of those mutants are currently in progress.