Characterization of the caspase family in zebrafish.

First discovered for their role in mediating programmed cell death and inflammatory responses, caspases have now emerged as crucial regulators of other cellular and physiological processes including cell proliferation, differentiation, migration, and survival. In the developing nervous system, for instance, the non-apoptotic functions of caspases have been shown to play critical roles in the formation of neuronal circuits by regulating axon outgrowth, guidance and pruning. How caspase activity is spatially and temporally maintained at sub-lethal levels within cells remains however poorly understood, especially in vivo. Thanks to its transparency and accessibility, the zebrafish offers the unique ability to directly visualize caspase activation in vivo. Yet, detailed information about the caspase family in zebrafish is lacking. Here, we report the identification and characterization of 19 different caspase genes in zebrafish, and show that caspases have diverse expression profiles from cleavage to larval stages, suggesting highly specialized and/or redundant functions during embryonic development.

EFN-4 functions in LAD-2-mediated axon guidance in Caenorhabditis elegans.

During development of the nervous system, growing axons rely on guidance molecules to direct axon pathfinding. A well-characterized family of guidance molecules are the membrane-associated ephrins, which together with their cognate Eph receptors, direct axon navigation in a contact-mediated fashion. InC. elegans, the ephrin-Eph signaling system is conserved and is best characterized for their roles in neuroblast migration during early embryogenesis. This study demonstrates a role for the C. elegans ephrin EFN-4 in axon guidance. We provide both genetic and biochemical evidence that is consistent with the C. elegans divergent L1 cell adhesion molecule LAD-2 acting as a non-canonical ephrin receptor to EFN-4 to promote axon guidance. We also show that EFN-4 probably functions as a diffusible factor because EFN-4 engineered to be soluble can promote LAD-2-mediated axon guidance. This study thus reveals a potential additional mechanism for ephrins in regulating axon guidance and expands the repertoire of receptors by which ephrins can signal.

The Caenorhabditis elegans Ephrin EFN-4 Functions Non-cell Autonomously with Heparan Sulfate Proteoglycans to Promote Axon Outgrowth and Branching.

The Eph receptors and their cognate ephrin ligands play key roles in many aspects of nervous system development. These interactions typically occur within an individual tissue type, serving either to guide axons to their terminal targets or to define boundaries between the rhombomeres of the hindbrain. We have identified a novel role for the Caenorhabditis elegans ephrin EFN-4 in promoting primary neurite outgrowth in AIY interneurons and D-class motor neurons. Rescue experiments reveal that EFN-4 functions non-cell autonomously in the epidermis to promote primary neurite outgrowth. We also find that EFN-4 plays a role in promoting ectopic axon branching in a C. elegans model of X-linked Kallmann syndrome. In this context, EFN-4 functions non-cell autonomously in the body-wall muscle and in parallel with HS modification genes and HSPG core proteins. This is the first report of an epidermal ephrin providing a developmental cue to the nervous system.