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PLoS One. 2019 Feb 12;14(2):e0211652. doi: 10.1371/journal.pone.0211652. eCollection 2019.

Conserved regulation of neurodevelopmental processes and behavior by FoxP in Drosophila.

Author information

1
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
2
Department of Biology, Faculty of Science, Western University, London, Ontario, Canada.
3
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany.
4
NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, Berlin, Germany.
5
Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Dresden, Germany.
6
Language and Genetics Department, Max Planck Institute of Psycholinguistics, Nijmegen, The Netherlands.
7
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.

Abstract

FOXP proteins form a subfamily of evolutionarily conserved transcription factors involved in the development and functioning of several tissues, including the central nervous system. In humans, mutations in FOXP1 and FOXP2 have been implicated in cognitive deficits including intellectual disability and speech disorders. Drosophila exhibits a single ortholog, called FoxP, but due to a lack of characterized mutants, our understanding of the gene remains poor. Here we show that the dimerization property required for mammalian FOXP function is conserved in Drosophila. In flies, FoxP is enriched in the adult brain, showing strong expression in ~1000 neurons of cholinergic, glutamatergic and GABAergic nature. We generate Drosophila loss-of-function mutants and UAS-FoxP transgenic lines for ectopic expression, and use them to characterize FoxP function in the nervous system. At the cellular level, we demonstrate that Drosophila FoxP is required in larvae for synaptic morphogenesis at axonal terminals of the neuromuscular junction and for dendrite development of dorsal multidendritic sensory neurons. In the developing brain, we find that FoxP plays important roles in α-lobe mushroom body formation. Finally, at a behavioral level, we show that Drosophila FoxP is important for locomotion, habituation learning and social space behavior of adult flies. Our work shows that Drosophila FoxP is important for regulating several neurodevelopmental processes and behaviors that are related to human disease or vertebrate disease model phenotypes. This suggests a high degree of functional conservation with vertebrate FOXP orthologues and established flies as a model system for understanding FOXP related pathologies.

PMID:
30753188
PMCID:
PMC6372147
DOI:
10.1371/journal.pone.0211652
[Indexed for MEDLINE]
Free PMC Article

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