Animals overexpressing tagged DBL-1 are more resistant to drugs, showing a dosedependent response to anesthetics by DBL-1. Using a novel microwave-based permeability assay for live animals and by genetically disrupting cross-linkages within the cuticle, we show that DBL-1 regulates cuticular barrier function. This physiological change in cuticular permeability is linked to the drug response phenotype displayed by DBL-1 pathway mutant animals. Loss of DBL-1 also permits tails to become entangled, forming ����wormstars����. This oriented aggregation is phenocopied in wild-type animals that have had their surface coat and lipids stripped, indicating that this phenotype in dbl-1 mutant animals is also cause by altered surface properties. Through ultrastructure studies, we identified a correlation of DBL-1 signaling level with substantial changes of cuticular layer organization and surface lipid amount. We propose that a common physiological mechanism, alteration of the cuticle, largely explains both the body length and drug response phenotypes, and underlies the ML130 worm-star aggregation defect we identified in dbl-1 loss-of-function populations. Furthermore, this work shows that BMP pathway signaling, which in mammals affects bone and other extracellular matrix growth and remodeling processes, also affects extracellular matrix in the invertebrate C. elegans, revealing a conserved function for the BMP family of cell signaling molecules. RNA interference was performed as previously described, with the exception that generations of animals were Azlocillin sodium salt continuously grown on IPTG-containing NGM plates that were seeded with bacteria expressing gene-specific double stranded RNA. Briefly, single colonies of HT115 bacteria containing relevant plasmids were selected, isolated, and grown overnight in carbenicillin, then induced for 4 to 5 hours with IPTG to express double stranded RNA from the plasmid. Each bacterial growth was spotted onto NGM plates containing carbenicillin and IPTG and dried. Animals were then transferred to and continuously cultured on NGM plates seeded with RNAi bacterial lawns at 15uC for use in either the drug sensitivity assays or fluorescent microscopy and imaging.