title: Novel Genes Involved in Controlling Specification of Drosophila FMRFamide Neuropeptide Cells.
abstract: The expression of neuropeptides is often extremely restricted in the nervous system, making them powerful markers for addressing cell specification . In the developing Drosophila ventral nerve cord, only six cells, the Ap4 neurons, of some 10,000 neurons, express the neuropeptide FMRFamide (FMRFa). Each Ap4/FMRFa neuron is the last-born cell generated by an identifiable and well-studied progenitor cell, neuroblast 5-6 (NB5-6T). The restricted expression of FMRFa and the wealth of information regarding its gene regulation and Ap4 neuron specification makes FMRFa a valuable readout for addressing many aspects of neural development, i.e., spatial and temporal patterning cues, cell cycle control, cell specification, axon transport, and retrograde signaling. To this end, we have conducted a forward genetic screen utilizing an Ap4-specific FMRFa-eGFP transgenic reporter as our readout. A total of 9781 EMS-mutated chromosomes were screened for perturbations in FMRFa-eGFP expression, and 611 mutants were identified. Seventy-nine of the strongest mutants were mapped down to the affected gene by deficiency mapping or whole-genome sequencing. We isolated novel alleles for previously known FMRFa regulators, confirming the validity of the screen. In addition, we identified novel essential genes, including several with previously undefined functions in neural development. Our identification of genes affecting most major steps required for successful terminal differentiation of Ap4 neurons provides a comprehensive view of the genetic flow controlling the generation of highly unique neuronal cell types in the developing nervous system.
authors.affiliation: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping SE-585 85, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bivik
authors.affiliation: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping SE-585 85, Sweden.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Bahrampour
authors.affiliation: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping SE-585 85, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Ulvklo
authors.affiliation: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping SE-585 85, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Nilsson
authors.affiliation: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping SE-585 85, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Angel
authors.affiliation: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping SE-585 85, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Fransson
authors.affiliation: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping SE-585 85, Sweden.
authors.forename: Erika
authors.initials: E
authors.lastname: Lundin
authors.affiliation: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping SE-585 85, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Renhorn
authors.affiliation: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping SE-585 85, Sweden stefan.thor@liu.se.
authors.forename: Stefan
authors.initials: S
authors.lastname: Thor
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics*; D019835:FMRFamide / Q000378:metabolism*; D005260:Female; D017344:Genes, Insect / Q000235:genetics*; D008297:Male; D016296:Mutagenesis; D009154:Mutation; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype
chemical_list: D019835:FMRFamide
keywords: CNS development; Drosophila; FMRFamide; forward genetic screening; neural cell fate specification