Developmental loss of neurofibromin across distributed neuronal circuits drives excessive grooming in Drosophila

Lanikea B King; Tamara Boto; Valentina Botero; Ari M Aviles; Breanna M Jomsky; Chevara Joseph; James A Walker; Seth M Tomchik

doi:10.1371/journal.pgen.1008920

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Developmental loss of neurofibromin across distributed neuronal circuits drives excessive grooming in Drosophila

Journal article

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Developmental loss of neurofibromin across distributed neuronal circuits drives excessive grooming in Drosophila

Lanikea B King, Tamara Boto, Valentina Botero, Ari M Aviles, Breanna M Jomsky, Chevara Joseph, James A Walker and Seth M Tomchik

PLoS genetics, Vol.16(7), pp.e1008920-e1008920

07/2020

DOI: 10.1371/journal.pgen.1008920

PMCID: PMC7398555

PMID: 32697780

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Abstract

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.

Animals

Cognition - physiology

Disease Models, Animal

Drosophila melanogaster - genetics

Drosophila Proteins - genetics

Embryo, Nonmammalian

Embryonic Development - genetics

Gene Knockdown Techniques

Grooming - physiology

Humans

Mutation - genetics

Nerve Tissue Proteins - genetics

Neurofibromatosis 1 - genetics

Neurofibromatosis 1 - pathology

Neurons - metabolism

Neurons - pathology

ras GTPase-Activating Proteins - genetics

Details

Title: Subtitle: Developmental loss of neurofibromin across distributed neuronal circuits drives excessive grooming in Drosophila
Creators: Lanikea B King - Scripps Research Institute
Tamara Boto - Scripps Research Institute
Valentina Botero - Scripps Research Institute
Ari M Aviles - Scripps Research Institute
Breanna M Jomsky - Scripps Research Institute
Chevara Joseph - Scripps Research Institute
James A Walker - Massachusetts General Hospital
Seth M Tomchik - Scripps Research Institute
Resource Type: Journal article
Publication Details: PLoS genetics, Vol.16(7), pp.e1008920-e1008920
DOI: 10.1371/journal.pgen.1008920
PMID: 32697780
PMCID: PMC7398555
NLM abbreviation: PLoS Genet
ISSN: 1553-7390
eISSN: 1553-7404
Publisher: Public Library Science
Grant note: R01 NS097237 / NINDS NIH HHS R21 NS096402 / NINDS NIH HHS
Language: English
Date published: 07/2020
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984303853602771

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