Identification of FoxP circuits involved in locomotion and object fixation in Drosophila.

Ottavia Palazzo,Björn Brembs,Mathias Rass

doi:10.1098/rsob.200295

Abstract

The FoxP family of transcription factors is necessary for operant self-learning, an evolutionary conserved form of motor learning. The expression pattern, molecular function and mechanisms of action of the Drosophila FoxP orthologue remain to be elucidated. By editing the genomic locus of FoxP with CRISPR/Cas9, we find that the three different FoxP isoforms are expressed in neurons, but not in glia and that not all neurons express all isoforms. Furthermore, we detect FoxP expression in, e.g. the protocerebral bridge, the fan-shaped body and in motor neurons, but not in the mushroom bodies. Finally, we discover that FoxP expression during development, but not adulthood, is required for normal locomotion and landmark fixation in walking flies. While FoxP expression in the protocerebral bridge and motor neurons is involved in locomotion and landmark fixation, the FoxP gene can be excised from dorsal cluster neurons and mushroom-body Kenyon cells without affecting these behaviours.

Highlights

The family of Forkhead Box (Fox) genes comprises a large number of transcription factors that share the evolutionary conserved forkhead/winged-helix DNAbinding domain [1]
The last two exons (7 and 8) are subjected to alternative splicing, leading to two different protein isoforms: isoform A (FoxP-iA), which results from splicing exon 6 to exon 7, and isoform B (FoxP-iB) where instead exon 8 is spliced to exon 6
We inserted the sequence of the yeast transcription factor Gal4 into exon 8, the exon which is exclusive to FoxP-isoform B (FoxP-iB)

Summary

Introduction

The family of Forkhead Box (Fox) genes comprises a large number of transcription factors that share the evolutionary conserved forkhead/winged-helix DNAbinding domain [1]. The function of FoxP genes in vocal learning appears to be evolutionary conserved as knock-outs of the zebra finch orthologue of human FOXP2 during the critical song learning period alters the structure of the crystallized song in the adults [14]. Such vocal learning is a form of motor learning that proceeds slowly from highly variable ‘babbling’ (in humans) and ‘subsong’ (in zebra finches) towards more stereotypic language and crystallized song, respectively. It was recently shown that, as in humans and zebra finches, in flies, FoxP is involved in such operant learning [18]

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Results

Conclusion