EGL-13/SoxD Specifies Distinct O2 and CO2 Sensory Neuron Fates in Caenorhabditis elegans

Animals harbor specialized neuronal systems that are used for sensing and coordinating responses to changes in oxygen (O-2) and carbon dioxide (CO2). In Caenorhabditis elegans, the O-2/CO2 sensory system comprises functionally and morphologically distinct sensory neurons that mediate rapid behavioral responses to exquisite changes in O-2 or CO2 levels via different sensory receptors. How the diversification of the O-2-and CO2-sensing neurons is established is poorly understood. We show here that the molecular identity of both the BAG (O-2/CO2-sensing) and the URX (O-2-sensing) neurons is controlled by the phylogenetically conserved SoxD transcription factor homolog EGL-13. egl-13 mutant animals fail to fully express the distinct terminal gene batteries of the BAG and URX neurons and, as such, are unable to mount behavioral responses to changes in O-2 and CO2. We found that the expression of egl-13 is regulated in the BAG and URX neurons by two conserved transcription factors-ETS-5(Ets factor) in the BAG neurons and AHR-1(bHLH factor) in the URX neurons. In addition, we found that EGL-13 acts in partially parallel pathways with both ETS-5 and AHR-1 to direct BAG and URX neuronal fate respectively. Finally, we found that EGL-13 is sufficient to induce O-2- and CO2-sensing cell fates in some cellular contexts. Thus, the same core regulatory factor, egl-13, is required and sufficient to specify the distinct fates of O-2 and CO2-sensing neurons in C. elegans. These findings extend our understanding of mechanisms of neuronal diversification and the regulation of molecular factors that may be conserved in higher organisms.