LIR-1 and PDTF-1 regulate the permeability barrier function of the C. elegans cuticle.

The cuticle of C. elegans presents the second largest surface area in the soma of worms. We have recently reported that the permeability barrier in the cuticle is dependent on six permeability-determining (PD) collagens and BLMP-1, a transcription factor. To identify additional regulators of cuticle permeability, we performed RNA interference for 286 transcription factors expressed in the C. elegans hypodermis and studied cuticle permeability to Hoechst 33258, a nucleic acid dye. Although the cuticle of wild type N2 strain is impermeable to this dye, RNAi of lir-1 or T26A8.1 (PDTF-1) caused permeability defect in the cuticle. LIR- 1 and PDTF-1 positively regulate expression of collagen and/or collagen processing enzymes. As a consequence, lir-1 and pdtf-1 RNAi also caused enhanced susceptibility to exogenous toxins such as paraquat, levamisole and ivermectin. Thus, LIR-1 and PDTF-1 are two hypodermis-specific transcriptional regulators of cuticle permeability.