Identifying Factors that Control Mechanoreceptor Neuron Development in C. elegans


Mechanosensation, or converting mechanical forces of external touch into electrical signals, is easily studied in Caenorhabditis elegans (C. elegans), a transparent nematode with a well-understood nervous system and a fully sequenced genome. The mechanosensory system mediates growth and development in most organisms; a lack of or defect in mechanosensory stimulation can lead to developmental delay in children, resulting in developmental disorders such as autism and spectrum disorders (ASDs) and Attention Deficit Disorder (ADD). Studying touch in the animal model C. elegans can elucidate the underlying neuronal mechanisms of touch and their developmental effects. In C. elegans, mechanoreceptor neurons (MRNs) detect touch, with three types that require the gene mec-3 (one of the LIM-homeodomain transcription factors) for their proper differentiation: touch receptor neurons (TRNs) (gentle touch), FLP neurons (tip of the head touch) and PVD neurons (harsh touch). While these three MRNs differentiate b the same transcription factor, each cell type’s differentiation produces distinct morphology and express different genes. FLPs exclusively express the sto-5 gene, while TRNs express the mec-17 gene. The genes that determine and distinguish FLP vs. TRN differentiation are currently limited to egl-44, egl-46 and alr-1. To identify additional genes needed for the differential expression of TRNs and FLPs, the wild-type strain (TU3813), with the FLP neurons labeled with sto-5p::gfp and the TRNs labeled with mec-17p::rfp, was mutated and animals with altered expression or neuronal morphology were isolated. While defects in both expression and morphology of the FLPs and TRNs were observed in six animals, only one animal’s mutation affecting TRN appearance was true-breeding. This morphological mutant exhibits abnormal TRN axon morphology, due to an autosomal recessive mutation. The mutant strain will be sequenced to identify the mutated gene, and the role of this gene in TRN and FLP differentiation.