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

Abstract

Animals harbor specialized neuronal systems that are used for sensing and coordinating responses to changes in oxygen (O2) and carbon dioxide (CO2). In Caenorhabditis elegans, 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. 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 O2 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 O2- 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 O2- 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.

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

“…The O 2 -sensing neuron fate of the BAG neurons, as assessed by expression of gcy-31 and gcy-33, is also defective in ets-5 and egl-13 mutant animals (Gramstrup Petersen et al 2013). However, the expression of these and other BAG terminal fate markers is not fully abrogated by concomitant loss of ets-5 and egl-13 (Gramstrup Petersen et al 2013). These studies suggest that parallel genetic programs exist that regulate the specification of the O 2 -and CO 2 -sensing BAG neuronal fates.…”

“…However, the expression of some BAG terminal fate markers, especially GCY-31 and GCY-33 that report O 2 -sensing fate, is only partially affected by simultaneous loss of ets-5 and egl-13 (Gramstrup Petersen et al 2013). In addition, the fully penetrant loss of GCY-9, a reporter for CO 2 -sensing fate, in ets-5 mutants is not observed in egl-13 mutant animals (Gramstrup Petersen et al 2013). We found that egl-46 does not affect the expression of ets-5 or egl-13 reporters, suggesting that it acts in a parallel manner to these transcription factors in specifying BAG neuronal fate (data not shown).…”

“…In addition, EGL-46 acts in a partially parallel pathway to that of EGL-13 and ETS-5 for the regulation of BAG terminal differentiation genes gcy-9, gcy-31, and gcy-33. In the absence of ets-5 and egl-13, two previously identified genes required for expression of the terminal differentiation genes in the BAG neurons, gcy-31 and gcy-33 expression is only partially affected (Guillermin et al 2011; Brandt et al 2012;Gramstrup Petersen et al 2013). Additionally, gcy-9 is partially affected in egl-13 mutant animals.…”

“…Whereas the soluble guanylyl cyclases GCY-31 and GCY-33 are expressed in the BAG neurons to mediate behavioral responses when O 2 levels decrease (Zimmer et al 2009). Previous studies have shown that the ETS domain-containing transcription factor ETS-5 is critical for CO 2 -sensing neuron fate through direct regulation of GCY-9 expression in the BAG neurons (Guillermin et al 2011; Brandt et al 2012;Gramstrup Petersen et al 2013). In addition, the Sox transcription factor EGL-13 is partially required for GCY-9 expression in the BAG neurons (Gramstrup Petersen et al 2013).…”

“…Previous studies have shown that the ETS domain-containing transcription factor ETS-5 is critical for CO 2 -sensing neuron fate through direct regulation of GCY-9 expression in the BAG neurons (Guillermin et al 2011; Brandt et al 2012;Gramstrup Petersen et al 2013). In addition, the Sox transcription factor EGL-13 is partially required for GCY-9 expression in the BAG neurons (Gramstrup Petersen et al 2013). Loss of either of these transcription factors causes defects in CO 2 avoidance behavior (Guillermin et al 2011; Brandt et al 2012;Gramstrup Petersen et al 2013).…”