title: Formation and specification of a Drosophila dopaminergic precursor cell.
abstract: Dopaminergic neurons play important roles in animal behavior, including motivation, reward and locomotion. The Drosophila dopaminergic H-cell interneuron is an attractive system for studying the genetics of neural development because analysis is focused on a single neuronal cell type. Here we provide a mechanistic understanding of how MP3, the precursor to the H-cell, forms and acquires its identity. We show that the gooseberry/gooseberry-neuro (gsb/gsb-n) transcription factor genes act to specify MP3 cell fate. It is proposed that single-minded commits neuroectodermal cells to a midline fate, followed by a series of signaling events that result in the formation of a single gsb(+)/gsb-n(+) MP3 cell per segment. The wingless signaling pathway establishes a midline anterior domain by activating expression of the forkhead transcription factors sloppy paired 1 and sloppy paired 2. This is followed by hedgehog signaling that activates gsb/gsb-n expression in a subgroup of anterior cells. Finally, Notch signaling results in the selection of a single MP3, with the remaining cells becoming midline glia. In MP3, gsb/gsb-n direct H-cell development, in large part by activating expression of the lethal of scute and tailup H-cell regulatory genes. Thus, a series of signaling and transcriptional events result in the specification of a unique dopaminergic precursor cell. Additional genetic experiments indicate that the molecular mechanisms that govern MP3/H-cell development might also direct the development of non-midline dopaminergic neurons.
authors.affiliation: Department of Biochemistry and Biophysics, Program in Molecular Biology and Biotechnology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Watson
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Crews
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D051155:Wnt1 Protein; C404810:gsb protein, Drosophila; C438191:gsb-n protein, Drosophila; C089449:sim protein, Drosophila; C074622:wg protein, Drosophila; C077245:hh protein, Drosophila