Chromatin Modulatory Proteins and Olfactory Receptor Signaling in the Refinement and Maintenance of Fruitless Expression in Olfactory Receptor Neurons

Abstract

During development, sensory neurons must choose identities that allow them to detect specific signals and connect with appropriate target neurons. Ultimately, these sensory neurons will successfully integrate into appropriate neural circuits to generate defined motor outputs, or behavior. This integration requires a developmental coordination between the identity of the neuron and the identity of the circuit. The mechanisms that underlie this coordination are currently unknown. Here, we describe two modes of regulation that coordinate the sensory identities of Drosophila melanogaster olfactory receptor neurons (ORNs) involved in sex-specific behaviors with the sex-specific behavioral circuit identity marker fruitless (fru). The first mode involves a developmental program that coordinately restricts to appropriate ORNs the expression of fru and two olfactory receptors (Or47b and Ir84a) involved in sex-specific behaviors. This regulation requires the chromatin modulatory protein Alhambra (Alh). The second mode relies on the signaling from the olfactory receptors through CamK and histone acetyl transferase p300/CBP to maintain ORN-specific fru expression. Our results highlight two feed-forward regulatory mechanisms with both developmentally hardwired and olfactory receptor activity-dependent components that establish and maintain fru expression in ORNs. Such a dual mechanism of fru regulation in ORNs might be a trait of neurons driving plastic aspects of sex-specific behaviors.

Transcriptional profiling of olfactory system development identifies distal antenna as a regulator of subset of neuronal fates

“…Because it has been previously shown that the onset of olfactory receptor expression begins around 40 hrs APF28, we were curious to see which, if any, ORs are expressed at this stage. We were able to detect OR transcripts at this stage, but they were expressed at much lower levels as compared to the adult stage (~2 orders of magnitude lower, Fig.…”

“…Upon selection of a “default” olfactory receptor within each sensillum, Notch signaling can relay this information to neighboring ORNs to suppress expression of the “default” receptor and select another olfactory receptor transcriptionally available in the lineage. These modifications might require chromatin regulation, as mutations in alhambra (alh), a chromatin modulator, result in acquisition of the default olfactory receptor expression at the expense of alternate olfactory receptors without modifying the target site of ORN axons in the antennal lobe28. There might be different spatial and temporal requirements of transcription factor and chromatin complexes for each sensilla lineage, as effects of alh mutants are restricted to only few sensilla28.…”

“…These modifications might require chromatin regulation, as mutations in alhambra (alh), a chromatin modulator, result in acquisition of the default olfactory receptor expression at the expense of alternate olfactory receptors without modifying the target site of ORN axons in the antennal lobe28. There might be different spatial and temporal requirements of transcription factor and chromatin complexes for each sensilla lineage, as effects of alh mutants are restricted to only few sensilla28. The expression patterns of both chromatin modulators and transcription factors in specific cell types remains an understudied area of olfactory system development.…”

Combinations of DIPs and Dprs control organization of olfactory receptor neuron terminals in Drosophila

“…caused by disruptions to ORN specification programs within at4 sensillum (44). To test whether ORN specification is altered in DIP-η knock down, we labeled Or47b and Or88a ORN cell bodies with RFP and GFP, respectively ( Fig S7D, E).…”

Mechanisms controlling diversification of olfactory sensory neuron classes

“…During development, a putative chromatin modulator Alhambra co-regulates the expression of fruitless and the olfactory receptors involved in sex specific behaviors [77]. Furthermore, fruitless expression is maintained in the adult through the activity of olfactory receptors, CamK signaling, and chromatin modulatory protein p300/CREB-binding protein to maintain sex specific ORN identity [77]. …”