Tuesday, April 30, 2019

New fly model for understanding cognitive deficits associated with disruption of FOXP genes

Castells-Nobau A, Eidhof I, Fenckova M, Brenman-Suttner DB, Scheffer-de Gooyert JM, Christine S, Schellevis RL, van der Laan K, Quentin C, van Ninhuijs L, Hofmann F, Ejsmont R, Fisher SE, Kramer JM, Sigrist SJ, Simon AF, Schenck A. Conserved regulation of neurodevelopmental processes and behavior by FoxP in Drosophila. PLoS One. 2019 Feb 12;14(2):e0211652. PMID: 30753188; PMCID: PMC6372147.

From the abstract: "FOXP proteins form a subfamily of evolutionarily conserved transcription factors ... 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 ... 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. ... At the cellular level, ... 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."

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