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Animals harbor specialized neuronal systems that are used for sensing and coordinating responses to changes in oxygen (O 2 ) and carbon dioxide (CO 2 ). In  Caenorhabditis elegans , the O 2 /CO 2  sensory system comprises functionally and morphologically distinct sensory neurons that mediate rapid behavioral responses to exquisite changes in O 2  or CO 2  levels via different sensory receptors. How the diversification of the O 2 - and CO 2 -sensing neurons is established is poorly understood. We show here that the molecular identity of both the BAG (O 2 /CO 2 -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 CO 2 . 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 CO 2 -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 CO 2 -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.

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