ABSTRACT
Basement membranes are thin sheets of specialized extracellular matrix molecules that are important for supplying mechanical support and for providing an interactive surface for cell morphology. Prior to secretion and assembly, basement membrane molecules undergo intracellular processing, which is essential for their function. We have identified several mutations in a procollagen processing enzyme, lysyl hydroxylase (let-268). The Caenorhabditis elegans lysyl hydroxylase is highly similar to the vertebrate lysyl hydroxylase, containing all essential motifs required for enzymatic activity, and is the only lysyl hydroxylase found in the C. elegans sequenced genome. In the absence of C. elegans lysyl hydroxylase, type IV collagen is expressed; however, it is retained within the type IV collagen-producing cells. This observation indicates that in let-268 mutants the processing and secretion of type IV collagen is disrupted. Our examination of the body wall muscle in these mutant animals reveals normal myofilament assembly prior to contraction. However, once body wall muscle contraction commences the muscle cells separate from the underlying epidermal layer (the hypodermis) and the myofilaments become disorganized. These observations indicate that type IV collagen is required in the basement membrane for mechanical support and not for organogenesis of the body wall muscle.
Subject(s)
Caenorhabditis elegans/enzymology , Caenorhabditis elegans/genetics , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics , Actin Cytoskeleton/metabolism , Amino Acid Sequence , Animals , Basement Membrane/growth & development , Caenorhabditis elegans/growth & development , Chromosome Mapping , Collagen/biosynthesis , Gene Expression , Genes, Helminth , Heparan Sulfate Proteoglycans/metabolism , Humans , Molecular Sequence Data , Muscle Contraction , Mutation , Procollagen/metabolism , Sequence Homology, Amino AcidABSTRACT
Two families, in which the children had been placed in foster care due to abuse and neglect by parents who had disabilities, were studied. In the first case, the mother was instructed in skills that our assessment suggested were important for her child's survival. The mother readily acquired and applied these skills, a fact reflected both in changes in her behavior and in changes in the child's well-being. In the second case, the parent's incremental resumption of child custody was made contingent upon completion of relevant parenting tasks. Initially, improvements in the completion of such tasks were evident, but over time and with the onset of militating factors, no further progress was made and all parental rights were terminated. The implications of these cases for behavior analysis and the effort to reunite and preserve families are discussed.
