The
bli-4 (I) gene of Caenorhabditis elegans had been previously defined by a single recessive mutation,
e937, which disrupts the structure of adult-stage cuticle causing the formation of fluid-filled separations of the cuticle layers, or blisters. We report the identification of 11 new alleles of
bli-4, all early larval lethals, including an allele induced by transposon mutagenesis. Nine of the lethal alleles failed to complement the blistered phenotype of
e937; two alleles,
s90 and
h754, complement
e937. The complementing alleles arrested development somewhat later than the noncomplementing alleles, which blocked just prior to hatching. We conclude that
bli-4 is a complex locus with an essential function late in embryogenesis. We investigated the blistered phenotype of
e937 through interactions with other mutations that alter worm morphology or cuticle structure. Recessive and dominant epistasis of several dumpy mutations over the blistered phenotype was observed. Using two heterochronic mutations that alter the developmental stage at which adult cuticle is expressed, we observed that adult worms that lack an adult-stage cuticle could not express blisters. However, late larval worms that expressed the adult cuticle did not express blisters either. It seems likely that the presence of the adult cuticle is necessary, but not sufficient, for blister expression. Blistering resulting from
e937 is more severe in trans to null alleles, indicating that
e937 is hypomorphic. We postulate that the adult-specific blistering is due to an altered or reduced function of
bli-4 gene product in the adult cuticle.(ABSTRACT TRUNCATED AT 250 WORDS)