Regulation of chemoreceptor gene expression in response to environmental or developmental cues provides a mechanism by which animals can alter their sensory responses. Here we demonstrate a role for the daf-7 TGF-␤ pathway in the regulation of expression of a subset of chemoreceptor genes in Caenorhabditis elegans. We describe a novel role of this pathway in maintaining receptor gene expression in the adult and show that the DAF-4 type II TGF-␤ receptor functions cell-autonomously to modulate chemoreceptor expression. We also find that the alteration of receptor gene expression in the ASI chemosensory neurons by environmental signals, such as levels of a constitutively produced pheromone, may be mediated via a DAF-7-independent pathway. Receptor gene expression in the ASI and ASH sensory neurons appears to be regulated via distinct mechanisms. Our results suggest that the expression of individual chemoreceptor genes in C. elegans is subject to multiple modes of regulation, thereby ensuring that animals exhibit the responses most appropriate for their developmental stage and environmental conditions.[Keywords: TGF-␤; C. elegans; chemosensory receptor; dauer] Supplemental material is available at http://www.genesdev.org.

Caenorhabditis elegans responds to its complex chemical environment using a small number of chemosensory neurons. Each of these neurons exhibits a unique sensory response repertoire. The developmental mechanisms that generate this diversity of function are largely unknown. Many C. elegans chemosensory neurons, including the AWA and ASG neurons, arise as lineal sisters of an asymmetric division. Here we describe the gene unc-130, which plays a role in the generation of the AWA and ASG neurons. In unc-130 mutants, the ASG neurons adopt the fate of the AWA neurons. unc-130 encodes a member of the forkhead domain family of transcription factors, and is expressed in the precursors to AWA and ASG neurons. Misexpression of unc-130 in the AWA neurons is partly sufficient to repress the AWA fate, but not to promote ASG fate. unc-130 also plays a role in the development of additional chemosensory neurons. Our experiments show that the ASG neurons share a developmental default state in common with three types of olfactory neurons. We propose that distinct cell fates and hence diversity of function in the chemosensory neurons of C. elegans are generated in a hierarchical manner, utilizing both lineage-dependent and independent mechanisms.

Chemosensory neuron diversity in C. elegans arises from the action of transcription factors that specify different aspects of sensory neuron fate. In the AWB and AWA olfactory neurons, the LIM homeobox gene lim-4 and the nuclear hormone receptor gene odr-7 are required to confer AWB and AWA-specific characteristics respectively, and to repress an AWC olfactory neuron-like default fate. Here, we show that AWA neuron fate is also regulated by a member of the LIM homeobox gene family, lin-11. lin-11 regulates AWA olfactory neuron differentiation by initiating expression of odr-7, which then autoregulates to maintain expression. lin-11 also regulates the fate of the ASG chemosensory neurons, which are the lineal sisters of the AWA neurons. We show that lin-11 is expressed dynamically in the AWA and ASG neurons, and that misexpression of lin-11 is sufficient to promote an ASG, but not an AWA fate, in a subset of neuron types. Our results suggest that differential temporal regulation of lin-11, presumably together with its interaction with asymmetrically segregated factors, results in the generation of the distinct AWA and ASG sensory neuron types. We propose that a LIM code may be an important contributor to the generation of functional diversity in a subset of olfactory and chemosensory neurons in C. elegans.