A Novel Role for the Zinc-Finger Transcription Factor EGL-46 in the Differentiation of Gas-Sensing Neurons in Caenorhabditis elegans

Oxygen (O(2)) and carbon dioxide (CO(2)) provoke distinct olfactory behaviors via specialized sensory neurons across metazoa. In the nematode C. elegans, the BAG sensory neurons are specialized to sense changes in both O(2) and CO(2) levels in the environment. The precise functionality of these neurons is specified by the coexpression of a membrane-bound receptor-type guanylyl cyclase GCY-9 that is required for responses to CO(2) upshifts and the soluble guanylyl cyclases GCY-31 and GCY-33 that mediate responses to downshifts in O(2). Expression of these gas-sensing molecules in the BAG neurons is partially, although not completely, controlled by ETS-5, an ETS-domain-containing transcription factor, and EGL-13, a Sox transcription factor. We report here the identification of EGL-46, a zinc-finger transcription factor, which regulates BAG gas-sensing fate in partially parallel pathways to ETS-5 and EGL-13. Thereby, three conserved transcription factors collaborate to ensure neuron type-specific identity features of the BAG gas-sensing neurons

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

<div><p></p><p>Animals harbor specialized neuronal systems that are used for sensing and coordinating responses to changes in oxygen (O₂) and carbon dioxide (CO₂). In <i>Caenorhabditis elegans</i>, the O₂/CO₂ sensory system comprises functionally and morphologically distinct sensory neurons that mediate rapid behavioral responses to exquisite changes in O₂ or CO₂ levels via different sensory receptors. How the diversification of the O₂- and CO₂-sensing neurons is established is poorly understood. We show here that the molecular identity of both the BAG (O₂/CO₂-sensing) and the URX (O₂-sensing) neurons is controlled by the phylogenetically conserved SoxD transcription factor homolog EGL-13. <i>egl-13</i> 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 O₂ and CO₂. We found that the expression of <i>egl-13</i> 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 O₂- and CO₂-sensing cell fates in some cellular contexts. Thus, the same core regulatory factor, <i>egl-13</i>, is required and sufficient to specify the distinct fates of O₂- and CO₂-sensing neurons in <i>C. elegans</i>. These findings extend our understanding of mechanisms of neuronal diversification and the regulation of molecular factors that may be conserved in higher organisms.</p></div