Atypical cadherin, Fat2, regulates axon terminal organization in the developing Drosophila olfactory receptor neurons.

The process of how neuronal identity confers circuit organization is intricately related to the mechanisms underlying neurodegeneration and neuropathologies. Modeling this process, the olfactory circuit builds a functionally organized topographic map, which requires widely dispersed neurons with the same identity to converge their axons into one a class-specific neuropil, a glomerulus. In this article, we identified Fat2 (also known as Kugelei) as a regulator of class-specific axon organization. In fat2 mutants, axons belonging to the highest fat2-expressing classes present with a more severe phenotype compared to axons belonging to low fat2-expressing classes. In extreme cases, mutations lead to neural degeneration. Lastly, we found that Fat2 intracellular domain interactors, APC1/2 (Adenomatous polyposis coli) and dop (Drop out), likely orchestrate the cytoskeletal remodeling required for axon condensation. Altogether, we provide a potential mechanism for how cell surface proteins' regulation of cytoskeletal remodeling necessitates identity specific circuit organization.

Social experience and pheromone receptor activity reprogram gene expression in sensory neurons.

Social experience and pheromone signaling in olfactory neurons affect neuronal responses and male courtship behaviors in Drosophila. We previously showed that social experience and pheromone signaling modulate chromatin around behavioral switch gene fruitless, which encodes a transcription factor necessary and sufficient for male sexual behaviors. Fruitless drives social experience-dependent modulation of courtship behaviors and physiological sensory neuron responses to pheromone; however, the molecular mechanisms underlying this modulation of neural responses remain less clear. To identify the molecular mechanisms driving social experience-dependent changes in neuronal responses, we performed RNA-seq from antennal samples of mutants in pheromone receptors and fruitless, as well as grouped or isolated wild-type males. Genes affecting neuronal physiology and function, such as neurotransmitter receptors, ion channels, ion and membrane transporters, and odorant binding proteins are differentially regulated by social context and pheromone signaling. While we found that loss of pheromone detection only has small effects on differential promoter and exon usage within fruitless gene, many of the differentially regulated genes have Fruitless-binding sites or are bound by Fruitless in the nervous system. Recent studies showed that social experience and juvenile hormone signaling co-regulate fruitless chromatin to modify pheromone responses in olfactory neurons. Interestingly, genes involved in juvenile hormone metabolism are also misregulated in different social contexts and mutant backgrounds. Our results suggest that modulation of neuronal activity and behaviors in response to social experience and pheromone signaling likely arise due to large-scale changes in transcriptional programs for neuronal function downstream of behavioral switch gene function.

The effect of Drosophila attP40 background on the glomerular organization of Or47b olfactory receptor neurons.

Bacteriophage integrase-directed insertion of transgenic constructs into specific genomic loci has been widely used by Drosophila community. The attP40 landing site located on the second chromosome gained popularity because of its high inducible transgene expression levels. Here, unexpectedly, we found that homozygous attP40 chromosome disrupts normal glomerular organization of Or47b olfactory receptor neuron (ORN) class in Drosophila. This effect is not likely to be caused by the loss of function of Msp300, where the attP40 docking site is inserted. Moreover, the attP40 background seems to genetically interact with the second chromosome Or47b-GAL4 driver, which results in a similar glomerular defect. Whether the ORN phenotype is caused by the neighbouring genes around Msp300 locus in the presence of attP40-based insertions or a second unknown mutation in the attP40 background remains elusive. Our findings tell a cautionary tale about using this popular transgenic landing site, highlighting the importance of rigorous controls to rule out the attP40 landing site-associated background effects.

Ant Olfaction: Smells Like an Insect, Develops Like a Mammal.

A detailed description of olfactory system development in ants reveals that - unlike in Drosophila and as in mammals - olfactory receptors may play a role, providing new insights into the developmental evolution of complex chemosensory systems.