A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity

Sensory neuron diversity is required for organisms to decipher complex environmental cues. In Drosophila, 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), which functions to increase 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, Bric-à-brac (Bab), Apterous (Ap) and Dachshund (Dac), constitute a functionally conserved transcription factor (TF) network, previously shown to pattern the segmentation of the leg, that patterns the developing olfactory tissue. 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 Time-course RNAseq across 4 developmental stages, inlcuding flies mutant for rotund gene (rn), heterozygotes and wildtype生物体解码复杂环境信号的过程依赖于感觉神经元的多样性。在果蝇中，嗅觉环境由50类不同的嗅觉受体神经元（olfactory receptor neuron, ORN）感知，这类神经元以组合聚类的方式分布于不同的感器亚型中。每一种感器亚型包含1~4种定型聚类的ORN身份，这些神经元均由单个多能感觉器官前体细胞（sensory organ precursor, SOP）经不对称分裂产生。目前尚不清楚每一类SOP如何获得独特的分化潜能，以解释ORN的多样性。此前本团队曾报道SOP分化程序的关键调控因子Rotund（Rn），其功能是通过在各独立感器类型的谱系中，从已有前体细胞中衍生出新的发育轨迹，从而增加ORN的多样性。本研究显示，Rn与BarH1/H2、Bric-à-brac（Bab）、Apterous（Ap）以及Dachshund（Dac）共同构成一个功能保守的转录因子（transcription factor, TF）网络；该网络此前被证实参与腿部分节的模式构建，此次研究发现其同样调控发育中的嗅觉组织的模式形成。在发育中的触角盘近远轴上，这些转录因子以独特组合形成同心环结构，从中筛选出具备不同ORN分化潜能的前体细胞。该网络内各因子间的交叉调控相互作用，建立了划分各前体区域的组合编码规则。对该网络的修饰可导致感器亚型与ORN库的多样性发生可预测的改变。基于本研究数据，我们提出一套分子图谱，该图谱用于界定覆盖4个发育阶段的时间序列RNA测序数据，实验样本包括rotund基因（rn）突变果蝇、杂合子果蝇与野生型果蝇。