[
FASEB J,
1994]
Two types of collagens have been identified in Caenorhabditis elegans corresponding to two types of extracellular matrix, the cuticle and basement membranes. Cuticle collagens are encoded by a developmentally regulated family of similar to 100 genes. Mutations in cuticle collagens can produce animals that are longer or shorter than normal and/or that are helically twisted. Mutations in different collagens can cause different morphological abnormalities, as can different mutations in the same collagen. Genetic interactions between collagen genes have been described and may identify collagens that interact to form the cuticle. Two basement membrane (type IV) collagen genes have been identified in C. elegans. They encode proteins similar in structure to vertebrate type IV collagen. One of the genes produces two alternatively spliced forms, one predominantly expressed in embryos and the other in larvae and adults, suggesting that embryonic basement membranes may have unique properties. Most mutations in the type IV genes cause embryonic lethality, indicating that normal basement membranes are required for embryogenesis. Temperature-sensitive mutations have been used to show that type IV collagen function is also required for larval development and adult fertility.
[
Annu Rev Genet,
1994]
All metazoans possess extracellular matrices (ECM) composed of complex assemblies of molecules with generally well conserved structures and functions. ECM play structural roles, providing scaffolds that organize and strengthen tissues, and instructional roles, influencing differentiation and development. Major ECM components include the collagens, a diverse family of fibrous proteins distinguished by their triple-helical coiled coil structure, other large glycoproteins, such as laminin, fibronectin and nidogen, and proteoglycans, proteins with attached glycosaminoglycan chains. For most ECM components, cell surface receptors have been identified that can mediate interactions between the cell and its ECM. The nematode Caenorhabditis elegans is an excellent system for studies of the structures and functions of ECM components, and their roles in development. C. elegans is the simplest metazoan in which detailed genetic analysis of the ECM can be performed. The complete cell lineage and detailed anatomical structure of the organism have been described. The simple life style of C. elegans allows animals with severe morphological and/or motility defects to survive and, because they are internally self-fertilizing hermaphrodites, even reproduce. These properties can simplify mutational analyses of genes encoding ECM components. Two major forms of ECM have been identified in C. elegans, the cuticle and basement membranes. The cuticle, or exoskeleton, covers the outside of the animal and lines the lumen of the pharynx. Basement membranes cover the pseudocoelomic faces of the pharynx, intestine, gonad, and hypodermis. There is no visible interstitial matrix between the cells within tissues, possibly because nearly all cells are adjacent to the cuticle or a basement membrane. This review focuses on studies of the ECM in C. elegans. The reader is referred to excellent recent reviews concerning related topics: collagens in other nematodes; mutations in human fibrillar collagens; mutations in human type IV collagen; composition
[
Sci STKE,
2000]
Notch proteins are receptors that are important in mediating several developmental processes. Notch receptors are activated upon binding transmembrane ligands, the DSL proteins. Notch is cleaved at several sites and activation of Notch leads to the cleavage of the intracellular domain, which then is translocated to the nucleus and regulates the transcription of target genes. Kramer discusses how binding of Notch to the DSL ligand, Delta, leads to cleavage and trans-endocytosis of the Notch extracellular domain into the Delta-expressing cell. This trans-endocytosis event contributes to the cleavage and release of the active Notch intracellular domain. The Perspective is accompanied by a movie illustrating the trans-endocytosis of Notch.