Engrailed induces expression of the secreted signaling protein Hedgehog in P cells. Hedgehog acts through Patched and Smoothened to control gene expression in A cells. Hedgehog

The Drosophila wing primordium is subdivided into adjacent territories called compartments (García-Bellido et al., 1973). Anteroposterior (AP) and dorsoventral (DV) compartment subdivisions are primarily established by the activity of the selector genes engrailed in P cells and apterous in D cells (reviewed by Blair, 1995). Short-range interactions between adjacent compartments induce expression of the signaling molecules Wingless (Wg) or Decapentaplegic (Dpp) along the compartment boundaries. Wg and Dpp organize pattern and growth of the wing anlage (Diaz-Benjumea and Cohen, 1995; Nellen et al., 1996; Zecca et al., 1996; Lecuit et al., 1996; Neumann and Cohen, 1997). One of the central features of compartments is that the cell populations that comprise them do not mix during development. Intermingling of cells between adjacent compartments has disastrous consequences in patterning and growth of the wing primordium (Milán and Cohen, 1999a). The onset of apterous expression in the early wing primordium induces expression of the Notch ligand Serrate in D cells and restricts expression of Delta, another Notch ligand, to V cells (Diaz-Benjumea and Cohen, 1995; Milán and Cohen, 2000). Dorsally expressed Serrate and ventrally expressed Delta activate Notch symmetrically in cells on both sides of the DV compartment boundary (Fig. 1A) (Diaz-Benjumea and Cohen, 1995; de Celis et al., 1996; Doherty et al., 1996). Expression of the glycosyltransferase Fringe makes D cells more sensitive to Delta and less sensitive to Serrate (Fleming et al., 1997; Panin et al., 1997; Brückner et al., 2000; Moloney et al., 2000; Munro and Freeman, 2000). Notch activation induces Wg expression in cells along the DV boundary. Later in development, an increase in dLMO (BX – FlyBase) levels reduces Ap activity in the wing primordium (Milán and Cohen, 2000). At this stage, another set of cell interactions takes over to maintain Wg expression along the DV boundary (Fig. 1B) (de Celis and Bray, 1997; Micchelli et al., 1997). Wg induces expression of Serrate and Delta in nearby D and V cells. Serrate and Delta signal back to activate Notch and thereby maintain Cut and Wg expression along the DV boundary. The persistent low level of Fringe in D cells continues to make D cells more sensitive to Delta and less sensitive to Serrate at this later stage (Milán and Cohen, 2000). At the time compartments were discovered, it was proposed that lineage restriction along the compartment boundaries depended on compartment specific expression of adhesion molecules that conferred differential cell affinities (GarcíaBellido et al., 1973). More recent studies have also indicated a role for cell communication at the compartment boundary. Engrailed induces expression of the secreted signaling protein Hedgehog in P cells. Hedgehog acts through Patched and Smoothened to control gene expression in A cells. Hedgehog signaling is needed to maintain segregation of A and P compartments (Blair and Ralston, 1997; Rodriguez and Basler, 1997) can fulfill this function because it is intrinsically asymmetric. Thus, it is easy to understand how Hh signaling 553 Development 130, 553-562 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00276