Layer-specific innervation is a major form of synaptic targeting in the central nervous system. In the Drosophila visual system, photoreceptors R7 and R8 connect to targets in distinct layers of the medulla, a ganglion of the optic lobe. We show here that Capricious (CAPS), a transmembrane protein with leucine-rich repeats (LRRs), is a layer-specific cell adhesion molecule that regulates photoreceptor targeting in the medulla. During the period of photoreceptor targeting, caps is specifically expressed in R8 and its target layer but not in R7 or its recipient layer. caps loss-of-function mutations cause local targeting errors by R8 axons, including layer change. Conversely, ectopic expression of caps in R7 redirects R7 axons to terminate in the CAPS-positive R8 recipient layer. CAPS promotes homophilic cell adhesion in transfected S2 cells. These results suggest that CAPS regulates layer-specific targeting by mediating specific axon-target interaction.

Domain boundary formation in development involves sorting of different types of cells into separate spatial domains. The segment boundary between tarsus 5 (Ta5) and the pretarsus (Pre) of the Drosophila leg initially appears at the center of the leg disc and progressively sharpens and expands to its final position, accompanied by down-regulation of the cell recognition molecule Capricious and Tartan and cell displacement from Ta5 to Pre across the boundary. Capricious and Tartan are controlled by transcription factor Bar and Al, and their loss of function leads to reduction of cell affinity to wild type neighbors and cell displacement activities. In addition, although the mutant cells formed Ta5/Pre boundary, its progression and sharpening were compromised. Cells overexpressing Capricious or Tartan became invasive within Ta5 and Pre, sometimes escaping the compartmental restriction of cell movement. Dynamic spatiotemporal regulation of cell affinity mediated by Capricious and Tartan is a key property of refinement of the Ta5/Pre boundary.

Growth, patterning, and apoptosis are mutually interactive during development. For example, cells that select an abnormal fate in a developing field are frequently removed by apoptosis. An important issue in this process that needs to be resolved is the mechanism used by cells to discern their correct fate from an abnormal fate. In order to examine this issue, we developed an animal model that expresses the dioxin receptor homolog Spineless (Ss) ectopically in the Drosophila wing. The presence of mosaic clones ectopically expressing ss results in a local transformation of organ identity, homeosis, from wing into a leg or antenna. The cells with misspecified fates subsequently activate c-Jun N-terminal kinase to undergo apoptosis in an autonomous or nonautonomous manner depending on their position within the wing, suggesting that a cell-cell interaction is, at least in some cases, involved in the detection of misspecified cells. Similar position dependence is commonly observed when various homeotic genes controlling the body segments are ectopically expressed. The autonomous and nonautonomous apoptosis caused by ss is regulated by a novel leucine-rich repeat family transmembrane protein, Fish-lips (Fili) that interacts with surrounding normal cells. These data support a mechanism in which the lack of some membrane proteins helps to recognize the presence of different cell types and direct these cells to an apoptotic fate in order to exclude them from the normal developing field.