title: Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila.
abstract: Neurofibromatosis I is a common genetic disorder that results in tumor formation, and predisposes individuals to a range of cognitive/behavioral symptoms, including deficits in attention, visuospatial skills, learning, language development, and sleep, and autism spectrum disorder-like traits. The nf1-encoded neurofibromin protein (Nf1) exhibits high conservation, from the common fruit fly, Drosophila melanogaster, to humans. Drosophila provides a powerful platform to investigate the signaling cascades upstream and downstream of Nf1, and the fly model exhibits similar behavioral phenotypes to mammalian models. In order to understand how loss of Nf1 affects motor behavior in flies, we combined traditional activity monitoring with video analysis of grooming behavior. In nf1 mutants, spontaneous grooming was increased up to 7x. This increase in activity was distinct from previously described dopamine-dependent hyperactivity, as dopamine transporter mutants exhibited slightly decreased grooming. Finally, we found that relative grooming frequencies can be compared in standard activity monitors that measure infrared beam breaks, enabling the use of activity monitors as an automated method to screen for grooming phenotypes. Overall, these data suggest that loss of nf1 produces excessive activity that is manifested as increased grooming, providing a platform to dissect the molecular genetics of neurofibromin signaling across neuronal circuits.
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458.
authors.forename: Lanikea B
authors.identifier: 0000-0002-2267-997X
authors.initials: LB
authors.lastname: King
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458 Laboratory of Glia Biology, Center for the Biology of Disease, VIB, 3000 Leuven, Belgium.
authors.forename: Marta
authors.initials: M
authors.lastname: Koch
authors.affiliation: Department of Metabolism and Aging, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458 Integrative Biology Graduate Program, Florida Atlantic University, Jupiter, Florida 33458.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Murphy
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458 SURF Program, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458.
authors.forename: Yoheilly
authors.initials: Y
authors.lastname: Velazquez
authors.affiliation: Department of Metabolism and Aging, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458.
authors.forename: William W
authors.initials: WW
authors.lastname: Ja
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458 stomchik@scripps.edu.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Tomchik
mesh_terms: D000818:Animals; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D056726:Genetic Association Studies; D006120:Grooming; D008297:Male; D009154:Mutation; D025542:Neurofibromin 1 / Q000235:genetics* / Q000378:metabolism*; D017440:Photoperiod; D012890:Sleep
chemical_list: D029721:Drosophila Proteins; D025542:Neurofibromin 1
keywords: Drosophila; Nf1; grooming; neurofibromatosis