A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity

Abstract

Sensory neuron diversity is required for organisms to decipher complex environmental cues. In Drosophila, the olfactory environment is detected by 50 different olfactory receptor neuron (ORN) classes that are clustered in combinations within distinct sensilla subtypes. Each sensilla subtype houses stereotypically clustered 1–4 ORN identities that arise through asymmetric divisions from a single multipotent sensory organ precursor (SOP). How each class of SOPs acquires a unique differentiation potential that accounts for ORN diversity is unknown. Previously, we reported a critical component of SOP diversification program, Rotund (Rn), increases ORN diversity by generating novel developmental trajectories from existing precursors within each independent sensilla type lineages. Here, we show that Rn, along with BarH1/H2 (Bar), Bric-à-brac (Bab), Apterous (Ap) and Dachshund (Dac), constitutes a transcription factor (TF) network that patterns the developing olfactory tissue. This network was previously shown to pattern the segmentation of the leg, which suggests that this network is functionally conserved. In antennal imaginal discs, precursors with diverse ORN differentiation potentials are selected from concentric rings defined by unique combinations of these TFs along the proximodistal axis of the developing antennal disc. The combinatorial code that demarcates each precursor field is set up by cross-regulatory interactions among different factors within the network. Modifications of this network lead to predictable changes in the diversity of sensilla subtypes and ORN pools. In light of our data, we propose a molecular map that defines each unique SOP fate. Our results highlight the importance of the early prepatterning gene regulatory network as a modulator of SOP and terminally differentiated ORN diversity. Finally, our model illustrates how conserved developmental strategies are used to generate neuronal diversity.

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

“…2). Our results are also consistent with previous reports that show that OR transcript expression level correlates with the number of neurons expressing a given receptor13. The early OR expression is also unlikely to be a by-product of the larval olfactory system as the larval olfactory system is not housed in the antennal disc13536 and none of the ORs expressed early are OR genes previously shown to be expressed in the larval olfactory system13536.…”

“…For every time point, we generated two biological replicates, each comprised of RNA pooled from >50 w1118 flies13. We first performed principal component analysis (PCA) to assess the sources of variation of transcripts across RNA datasets from 4 developmental stages (Fig.…”

“…The antennal disc undergoes three major phases of development: prepatterning, precursor selection, and neurogenesis12. The epithelial cells of the antennal disc are initially patterned by gene regulatory networks that establish multiple ring-like fields with different and restricted differentiation potentials13141516. Each field gives rise to the precursors that will generate different combinations of ORNs.…”

Age influences the olfactory profiles of the migratory oriental armyworm mythimna separate at the molecular level

“…In Heliconius melpomene , the IR75d gene is highly expressed across various tissues and sexes [63]. In D. melanogaster , IR75d is expressed in three different OSNs that are housed in three coeloconic sensilla (ac1, ac2, and ac4) [64] and is the only ORN class that occurs in more than one sensilla subtype [65]. In addition, IR75d is co-expressed with IR84a and IR76a in ac4 sensilla [66].…”

Genetic mapping of male pheromone response in the European corn borer identifies candidate genes regulating neurogenesis

“…The protein encoded by bab possesses a BTB domain also found in the Drosophila genes tramtrack and Broad-Complex (55). Moreover, bab was recently found to interact with other transcription factors in a network that patterns the developing olfactory tissue in D. melanogaster (56).…”