C. elegans is equipped with highly specialized sensory neurons that enable the animal to accurately sense its environment. Our lab is interested in understanding how the unique functions of individual sensory neurons are specified during development. In order to identify genes required for the development of these diverse neuron types, we have taken the approach of isolating mutants that exhibit altered expression of sensory neuron-specific markers. This strategy has allowed the identification of cascades of transcription factors required to define the identities of specific sensory neuron types, including the AWA olfactory and the AFD thermosensory neurons. My goal is to understand the developmental mechanisms by which the AWB olfactory neurons are specified. Previous work has demonstrated that expression of the LIM homeodomain transcription factor LIM-4 in the AWB neurons is crucial for their development. In
lim-4 mutants, the AWB neurons lose AWB-specific characteristics, and instead adopt a default sensory neuron fate (Sagasti et al. 1999). We isolated an allele of the gene
ceh-37 in a screen for mutants that fail to express an AWB-specific odorant receptor.
ceh-37 appears to act upstream of
lim-4, since in
ceh-37 mutants,
lim-4 expression in the AWB neurons is variably lost. Interestingly, although in
lim-4 mutants the AWB neurons lose all neuron-specific characteristics including the ability to fill with DiO, the AWB neurons retain the ability to dye-fill in
ceh-37 null mutants. In addition, unlike
lim-4 mutants, the AWB neurons in
ceh-37 mutant animals do not adopt default olfactory neuron characteristics. This suggests that CEH-37 may act to regulate the expression of
lim-4 as well as additional factors required for AWB development.
ceh-37 encodes an OTX-like homeodomain transcription factor. It is one of three similar otx-related genes encoded by the C. elegans genome. OTX-related proteins have been implicated in the patterning of anterior structures in vertebrates, Drosophila and also in the development of the C. elegans AFD thermosensory neurons. The otx homolog
ttx-1 has been shown to be both necessary and sufficient to specify the fate of the AFD thermosensory neurons in C. elegans (Satterlee et al. 2001). Thus, the development of both the AFD and the AWB sensory neurons require the function of closely related genes. CEH-37 is expressed broadly in the early embryo although its expression is restricted to the excretory cell in larval and adult stages. Its embryonic expression implicates an early role for CEH-37 in the development of the AWB neurons. We have shown that expression of CEH-37 specifically in the amphid neurons is sufficient to rescue the AWB defects of
ceh-37 mutants. Surprisingly, we found that amphid-specific expression of any of the three C. elegans OTX-like genes is sufficient to rescue the AWB development defects of
ceh-37 mutants. While misexpression of CEH-37 is not sufficient to induce ectopic expression of AWB specific genes,
ceh-37 misexpression results in the ectopic expression of AFD-like characteristics in some neurons. The conservation of function between CEH-37 and TTX-1 suggests that precise regulation of the spatial and temporal expression of these otx-like genes during development is essential in order to ensure the correct development and function of the C. elegans sensory neurons.