Cytonemes

Felipe-Andrés Ramírez-Weber, Thomas B Kornberg
1999 Cell  
Tabata and Kornberg, 1994). The Dpp protein is also secreted. Dpp is believed to embody the activity Summary of the A/P signaling center (Capdevila and Guerrero, 1994; Zecca et al., 1995) by using a concentration-Wing imaginal disc cells in Drosophila develop by using dependent mechanism to control the expression of variinformation received from a signaling center associous target genes (Lecuit et al., 1996; Nellen et al., 1996; ated with the anterior/posterior compartment border. Tsuneizumi et
more » ... al., 1997). Although Dpp is assumed to We show here that disc cells have thin, actin-based form a concentration gradient, there is no direct eviextensions (cytonemes) that project to this signaling dence for its distribution in discs. Nevertheless, its target center. Cytonemes can be induced when cells from genes are expressed in roughly symmetric patterns with the lateral flanks of a wing disc are cultured next to respect to the A/P border, and as a consequence, A and cells from the A/P border or next to a source of fibro-P cells in the fly wing differentiate particular structures at blast growth factor. Mouse limb bud cells also grow prescribed distances from the border. Since cells at projections during a brief culture period, indicating equivalent distances on either side of the compartment that cytonemes are an attribute of both vertebrate and border have the capacity to make identical structures invertebrate cells. We suggest that cytonemes may (Garcia-Bellido and Santamaria, 1972; Lawrence and be responsible for some forms of long-range cell-cell Morata, 1976), they are said to behave as though polarcommunication. ized with opposite orientations. This use of the term polarity is unrelated to apical/basal or dendritic/axonal Introduction polarity, or to the "planar polarity" that orients the hair and bristle structures that epidermal cells make. It has Cells use a variety of mechanisms to communicate over had no known morphological manifestation. long distances. Information can be transmitted to distant In addition to defining where key regulatory genes organs by small proteins or organic molecules that travel are expressed and generating an associated signaling to specific receptors at target sites. Alternatively, inforcenter, the A/P compartment borders also confine imamation can be transmitted by long cellular extensions ginal disc cells to either side (Garcia-Bellido et al., 1973, such as axons. These neuronal processes transduce 1976; Morata and Lawrence, 1975, 1978; Steiner, 1976; signals between the nerve terminal and cell body by Lawrence et al., 1979; Kornberg, 1981; Struhl, 1981) and actively transporting endocytosed ligands or by concan retard the diffusion of small organic molecules (Weir ducting electrical currents. Long distance communicaand Lo, 1982) . This partial catalog of the functions assotion also is involved in the development of epithelial ciated with the compartment border illustrates some cells, since their growth is controlled by signaling cenof the ways in which cells at the compartment border ters that can be located more than 100 m away. Howgenerate spatial guideposts during development. It seems ever, the mechanisms that link these cells to the signalreasonable to predict that these cells may have special ing centers are not understood. structures to perform these tasks, but no distinguishing In the Drosophila wing imaginal disc, the principal morphological structures that might endow them with signaling center is located on the anterior side of the their special functions have been reported. A/P compartment border that bisects the disc. It is cre- The study described here was guided by our interest ated by signals emanating from the A/P compartment in learning more about the nature of the border cells. In border and is defined operationally by its roles both in particular, we have been examining how the Hh and regulating growth and patterns of gene expression and Dpp proteins signal target cells. Although the influence in prescribing the placement of each pattern element of Dpp extends to the edges of the wing disc (Capdevila (Basler and Struhl, 1994; Tabata and Kornberg, 1994). and Guerrero, 1994; Zecca et al., 1995) and Hh can signal Two proteins, Hedgehog (Hh) and Decapentaplegic across long distances as well (Chen and Struhl, 1996), (Dpp), carry out the respective signaling functions of the these proteins share an unexpected characteristic: they compartment border and the signaling center it gendo not move efficiently in the extracellular environment. erates. Current evidence indicates that the active form of Hh has Hh is one of a small group of genes whose domain cholesterol covalently bound at its C terminus (Porter of expression is delimited by A/P compartment borders. et al., 1996) and an N terminus that is palmitoylated It is expressed by all P compartment cells (Tabata et (Pepinsky et al., 1998). Both modifications are likely to al., 1992) and produces a secreted protein (Porter et al., anchor Hh in the membrane of the cell in which it is made. The Dpp homolog, TGF␤, binds to extracellular
doi:10.1016/s0092-8674(00)80771-0 pmid:10367889 fatcat:2lmezitpobekfg3tpamgdduvke