Wing-to-Leg Homeosis by Spineless Causes Apoptosis Regulated by Fish-lips, a Novel Leucine-Rich Repeat Transmembrane Protein

Abstract

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.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://mcb.asm.org/.

ACKNOWLEDGMENTS

We thank R. Barrio, S. Campbell, S. T. Crews, A. García-Bellido, B. A. Hay, Y. Hiromi, Y. H. Inoue, K. Irvine, W. Janning, E. Martín-Blanco, A. Martinez-Arias, A. Nose, S. Noselli, C. Rauskolb, M. Shinza-Kameda, G. Struhl, K. Takahashi, and D. Yamamoto, Bloomington Stock Center, and GETDB (GAL4-Enhancer Trap Data Base) in the National Institute of Genetics in Japan, for the fly strains; R. Barrio, G. Campbell, S. B. Carroll, D. Duncan, A. Nose, M. Shinza-Kameda, and P. ten Dijke, Developmental Studies Hybridoma Bank, Iowa University, and Idun Pharmaceutical, Inc., for antibodies; J. Kim and Y. Lee for technical advice; and Y. Aoki and O. Habara for technical assistance.

This study was supported by grants from the Japan Science and Technology Agency; the Ministry of Education, Science, Sports, and Culture in Japan (to T.A.-Y.); and NIH and the Human Frontier Science Program (to H.N.). M.B.O. is an Investigator of the Howard Hughes Medical Institute.