title: Modulation of light-driven arousal by LIM-homeodomain transcription factor Apterous in large PDF-positive lateral neurons of the Drosophila brain.
abstract: Apterous (Ap), the best studied LIM-homeodomain transcription factor in Drosophila, cooperates with the cofactor Chip (Chi) to regulate transcription of specific target genes. Although Ap regulates various developmental processes, its function in the adult brain remains unclear. Here, we report that Ap and Chi in the neurons expressing PDF, a neuropeptide, play important roles in proper sleep/wake regulation in adult flies. PDF-expressing neurons consist of two neuronal clusters: small ventral-lateral neurons (s-LNvs) acting as the circadian pacemaker and large ventral-lateral neurons (l-LNvs) regulating light-driven arousal. We identified that Ap localizes to the nuclei of s-LNvs and l-LNvs. In light-dark (LD) cycles, RNAi knockdown or the targeted expression of dominant-negative forms of Ap or Chi in PDF-expressing neurons or l-LNvs promoted arousal. In contrast, in constant darkness, knockdown of Ap in PDF-expressing neurons did not promote arousal, indicating that a reduced Ap function in PDF-expressing neurons promotes light-driven arousal. Furthermore, Ap expression in l-LNvs showed daily rhythms (peaking at midnight), which are generated by a direct light-dependent mechanism rather than by the endogenous clock. These results raise the possibility that the daily oscillation of Ap expression in l-LNvs may contribute to the buffering of light-driven arousal in wild-type flies.
authors.affiliation: Department of Biological Sciences, Graduate school of science &engineering, Tokyo Metropolitan University, Tokyo, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Shimada
authors.affiliation: Department of Biological Sciences, Graduate school of science &engineering, Tokyo Metropolitan University, Tokyo, Japan.
authors.forename: Show
authors.initials: S
authors.lastname: Inami
authors.affiliation: Department of Biological Sciences, Graduate school of science &engineering, Tokyo Metropolitan University, Tokyo, Japan.
authors.forename: Shoma
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Anesthesia, University of Iowa, Iowa City, Iowa, United States of America.|Interdisciplinary Graduate Programs in Genetics and Neuroscience, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kitamoto
authors.affiliation: Department of Biological Sciences, Graduate school of science &engineering, Tokyo Metropolitan University, Tokyo, Japan.
authors.forename: Takaomi
authors.initials: T
authors.lastname: Sakai
mesh_terms: D000818:Animals; D001143:Arousal / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics; D004331:Drosophila melanogaster; D060850:LIM-Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D008027:Light; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D060850:LIM-Homeodomain Proteins; D009479:Neuropeptides; D014157:Transcription Factors; C074459:ap protein, Drosophila; C113883:pdf protein, Drosophila