The external skeleton of nematodes, also called the cuticle, is a complex, multi-layered extracellular matrix secreted by underlying epidermal cells. The cuticle maintains the shape of the worm, provides a frame for the attachment of muscles, protects the organism from desiccation or injury, and participates in the uptake of nutrients. The various layers of the cuticle perform distinct functions and, accordingly, consist of different molecular assemblies. Further, the precise biochemical composition and ultrastructure of the cuticle changes with every molt, presumably to accommodate the needs of the developing organism.

At every molt, the epidermis detaches from the old cuticle (apolysis) and secretes a new one; outermost layers first. Particular components of the old cuticle are likely degraded and recycled. Points of adhesion between the cuticle, the epidermis, and the basement membrane of the underlying muscle are also remodeled. When the new cuticle is functional, the animal can safely escape the old skeleton (ecdyse).

The major goal of our laboratory is to define the signaling pathways and enzymatic cascades that promote remodeling of the epidermis and related extracellular matrices during molting. Because collagens are the predominant structural components of the cuticle, similar to human skin and connective tissue, findings related to the molecular mechanisms of molting will apply directly to matrix biology in vertebrates.

We are currently investigating the functions of particular genes essential for release of the old cuticle and exploring potential regulatory relationships among the corresponding proteins. We are most interested in conserved secretory proteins implicated in ECM homeostasis in vertebrates, including the low-density lipoprotein receptor-like protein LRP 1, particular matricellular proteases and anti-proteases, and the fibrillin homolog FBN 1. We expect our ongoing studies of molting to reveal conserved mechanisms important for normal development, wound healing, the metastasis of tumors, and the pathogenesis of Marfan syndrome in humans.