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PMID:18516287

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Citation

Berger, J, Senti, KA, Senti, G, Newsome, TP, Asling, B, Dickson, BJ and Suzuki, T (2008) Systematic identification of genes that regulate neuronal wiring in the Drosophila visual system. PLoS Genet. 4:e1000085

Abstract

Forward genetic screens in model organisms are an attractive means to identify those genes involved in any complex biological process, including neural circuit assembly. Although mutagenesis screens are readily performed to saturation, gene identification rarely is, being limited by the considerable effort generally required for positional cloning. Here, we apply a systematic positional cloning strategy to identify many of the genes required for neuronal wiring in the Drosophila visual system. From a large-scale forward genetic screen selecting for visual system wiring defects with a normal retinal pattern, we recovered 122 mutations in 42 genetic loci. For 6 of these loci, the underlying genetic lesions were previously identified using traditional methods. Using SNP-based mapping approaches, we have now identified 30 additional genes. Neuronal phenotypes have not previously been reported for 20 of these genes, and no mutant phenotype has been previously described for 5 genes. The genes encode a variety of proteins implicated in cellular processes such as gene regulation, cytoskeletal dynamics, axonal transport, and cell signalling. We conducted a comprehensive phenotypic analysis of 35 genes, scoring wiring defects according to 33 criteria. This work demonstrates the feasibility of combining large-scale gene identification with large-scale mutagenesis in Drosophila, and provides a comprehensive overview of the molecular mechanisms that regulate visual system wiring.

Links

PubMed PMC2377342 Online version:10.1371/journal.pgen.1000085

Keywords

Animals; Axons/physiology; Cloning, Molecular; Drosophila/genetics; Drosophila/physiology; Drosophila Proteins/genetics; Mutation; Nervous System/metabolism; Phenotype; Polymorphism, Single Nucleotide; Retina/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:LAR

involved_in

GO:0007411: axon guidance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:JNK

involved_in

GO:0007411: axon guidance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PROF

involved_in

GO:0007411: axon guidance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9Y1L3

involved_in

GO:0007411: axon guidance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PTP69

involved_in

GO:0007411: axon guidance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:RB27C

involved_in

GO:0007411: axon guidance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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