Developmental loss of neurofibromin across distributed neuronal circuits drives excessive grooming in Drosophila
Autoři:
Lanikea B. King aff001; Tamara Boto aff001; Valentina Botero aff001; Ari M. Aviles aff001; Breanna M. Jomsky aff001; Chevara Joseph aff001; James A. Walker aff003; Seth M. Tomchik aff001
Působiště autorů:
Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida, United States of America
aff001; Honors College, Florida Atlantic University, Jupiter, Florida, United States of America
aff002; Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Cambridge, Massachusetts, United States of America
aff003
Vyšlo v časopise:
Developmental loss of neurofibromin across distributed neuronal circuits drives excessive grooming in Drosophila. PLoS Genet 16(7): e32767. doi:10.1371/journal.pgen.1008920
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008920
Souhrn
Neurofibromatosis type 1 is a monogenetic disorder that predisposes individuals to tumor formation and cognitive and behavioral symptoms. The neuronal circuitry and developmental events underlying these neurological symptoms are unknown. To better understand how mutations of the underlying gene (NF1) drive behavioral alterations, we have examined grooming in the Drosophila neurofibromatosis 1 model. Mutations of the fly NF1 ortholog drive excessive grooming, and increased grooming was observed in adults when Nf1 was knocked down during development. Furthermore, intact Nf1 Ras GAP-related domain signaling was required to maintain normal grooming. The requirement for Nf1 was distributed across neuronal circuits, which were additive when targeted in parallel, rather than mapping to discrete microcircuits. Overall, these data suggest that broadly-distributed alterations in neuronal function during development, requiring intact Ras signaling, drive key Nf1-mediated behavioral alterations. Thus, global developmental alterations in brain circuits/systems function may contribute to behavioral phenotypes in neurofibromatosis type 1.
Klíčová slova:
Behavior – Central nervous system – Drosophila melanogaster – Neural pathways – Neurofibromatosis type 1 – Neurons – Ras signaling – RNA interference – Genetics
Zdroje
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