Wing-to-Leg homeosis by spineless causes apoptosis regulated by Fish-lips, a novel leucine-rich repeat transmembrane protein
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Published on: May 21, 2014
Takashi Adachi-Yamada1, Toshiyuki Harumoto, Kayoko Sakurai
1Department of Earth and Planetary System Sciences, Graduate School of Science and Technology, Kobe University, Kobe 657-8501, Japan. yamadach@kobe-u.ac.jp
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.
Insights
Cells identify and eliminate abnormal fates during development through apoptosis. This study reveals how Drosophila cells distinguish correct fates from abnormal ones, involving cell-cell interactions and the Fish-lips protein.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- Cell fate determination and apoptosis are crucial for proper development.
- Understanding how cells recognize and eliminate misspecified cells is essential for developmental processes.
Purpose of the Study:
- To investigate the mechanisms by which cells discern correct fates from abnormal ones during development.
- To explore the role of ectopic Spineless (Ss) expression in inducing cell fate changes and apoptosis in Drosophila wings.
Main Methods:
- Development of a Drosophila animal model with ectopic Spineless (Ss) expression in the wing.
- Analysis of mosaic clones exhibiting homeotic transformations (wing to leg/antenna).
- Investigation of c-Jun N-terminal kinase activation and apoptosis, examining autonomous and nonautonomous mechanisms.
Main Results:
- Ectopic Spineless (Ss) expression caused homeotic transformations and subsequent apoptosis of misspecified cells.
- Apoptosis occurred autonomously or nonautonomously, influenced by cell position, suggesting cell-cell interactions.
- The leucine-rich repeat transmembrane protein Fish-lips (Fili) was identified as a regulator of Ss-induced apoptosis, interacting with surrounding normal cells.
Conclusions:
- A mechanism exists where cells recognize misspecified neighbors by the absence of specific membrane proteins.
- This recognition triggers apoptosis to remove aberrant cells, ensuring developmental field integrity.
- Fish-lips (Fili) plays a key role in mediating this cell-cell interaction-dependent apoptotic response.
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