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

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.

Wings of Change: aPKC/FoxP-dependent plasticity in steering motor neurons underlies operant selflearning inDrosophila

“…FoxP was shown to be important for normal development (Castells-Nobau et al, 2019; Palazzo et al, 2020). Strong motor impairments were reported after a developmental FoxP knock-out, for instance rendering the animals unable to fly (see above).…”

“…Second, FoxP may exert its effects as a developmental regulator, being crucial for the development of the circuits mediating operant self-learning. As the developmental role of FoxP genes is well documented (Takahashi et al, 2009; Bowers et al, 2014; Rocca et al, 2017; Castells-Nobau et al, 2019; Co et al, 2020; Palazzo et al, 2020) and there are few domains in the gene that would lend themselves for a hypothetical cytosolic function, the latter hypothesis appeared more plausible. The result that adult knockout of FoxP had no immediate effect in operant self-learning (Fig.…”

“…Thus, these data suggest that baz is indeed not directly involved in me- ing operant self-learning. As the developmental role of FoxP genes is well documented (7,14,72,82,149,150) and there are few domains in the gene that would lend themselves for a hypothetical cytosolic function, the latter hypothesis appeared more plausible. The result that adult knockout of FoxP had no immediate effect in operant self-learning (Fig.…”

Sensitivity to expression levels underlies differential dominance of a putative null allele of the Drosophila tßh gene in behavioral phenotypes

“…The GAL4/UAS system does not provide for sufficient control of gene expression levels to accommodate more unconventional modes of inheritance. In fact, in some cases, the basal promoter used in the creation of the GAL4 line may decide about the success or failure of an experiment [ 94 ].…”

“…While pleiotropy was not found to be universal [ 8 ], it is not known how many genes in Drosophila are pleiotropic, nor how many of them display differential dominance. However, we have recently observed differential dominance in at least 1 other gene, the transcription factor FoxP [ 94 ].…”