Cytonemes extend their reach.

Cytonemes are specialized filopodia, first described in the Drosophila wing imaginal disc, that were proposed to mediate long distance signalling during development. A recent report from Barna and colleagues (Sanders et al, 2013) published in Nature shows that cytonemes in the chick limb bud carry SHH signalling proteins out to signal receiving cells, thus highlighting their evolutionarily conserved roles in cell–cell communication. Our textbooks inform us that long distance signalling by animal cells is carried out in either of two ways. One, specific for neurons, involves signal exchange at sites of direct contact. The cell body of a neuron can be far from target cells (even metres away), but neurons extend processes that can bridge the distance to the target cell. Non-neuronal cells, in contrast, are hemmed in by their neighbours, their contacts limited to nearest neighbours, and they use the other mode: signal release at the surface of signal-producing cells, followed by dispersion in extracellular fluid so that released signals eventually bind to receptors on target cells. This clean dichotomy of form and function that has long been thought to distinguish neurons from all other cells appears no longer valid. Several lines of evidence now show that non-neuronal cells also extend asymmetric processes—filopodia—that mediate long-range signalling. Filopodia are rod-like projections that extend from the periphery of many type of cells (for review, see Faix et al, 2009). They contain bundles of actin filaments, are highly dynamic and flexible, and can appear to surf over the surface of cells. They are present at nerve growth cones, where they project towards sources of chemotactic signals and are presumed to have a sensory, pathfinding function. Some tumour cells have such processes (a.k.a. invadopodia), which may be involved in ECM degradation and intravasation during metastasis. They are present in cells at the leading edge of epithelial sheets, in fibroblasts, myoblasts, glia, and dendritic cells. Although the functions of these filopodia have not been confirmed—loss-of-function studies are complicated by general effects on the cytoskeleton—the settings in which they are found suggest roles in migration, adhesion, and cell–cell recognition. Nevertheless, their presence in so many cell types informs us that neurons are not unique in making projections that reach into the surrounding milieu. Cytonemes are filopodia that are specialized for transmitting signalling proteins between communicating cells. The idea is based on a model in which filopodia are structurally and functionally diverse, with a subset dedicated and designed for juxtacrine signalling between distant cells. The term cytoneme was coined to highlight this specialized functionality (Ramirez-Weber and Kornberg, 1999). Filopodia with apparent sensory function had been observed previously in various contexts: thin, dynamic filopodia extend across sea urchin embryos, appearing to explore and perhaps pattern distant sheets of cells (reviewed in McClay, 1999), and anthropomorphic descriptions of neuronal growth cone