Apoptosis-defective flies (bottom) lack a well-defined leg joint.


Aleg that doesn't bend is not much use. To make space for joints in the fruit fly limb, a thin band of cells are carved out by apoptosis, according to a new study by Cristina Manjón, Ernesto Sánchez-Herrero, and Magali Suzanne (Autonomous University of Madrid, Spain). The team shows that a sharp switch in morphogen signaling determines which cells get eliminated.

The morphogen in question is decapentaplegic (Dpp). In developing flies, it defines where and in which direction the legs should grow. Manjon et al. now find that, later on, Dpp initiates the formation of joints in the distal segments of the fly leg.

Across the would-be joints, Dpp signaling activity abruptly switches from high to low. At this transition point, a narrow band of cells undergoes apoptosis. Mutants that lack the signaling boundary due to either uniformly high or uniformly low Dpp activity fail to induce apoptosis and do not form bendable joints. Thus it is not the amount of Dpp protein but the switch in Dpp signaling itself which activates cell death.

Although the fly leg has eight joints, the five furthest from the body are the only ones where Dpp gradient-dependent apoptosis seems to be necessary for flexibility. Suzanne speculates that joint formation in the early segments may depend on alternate pathways, just as different gene expression programs drive the formation of different leg sections.

The group is now trying to decipher how the Dpp signal is suddenly shut off and how the transition between high and low Dpp is sensed by the apoptosis pathway. They propose that an interaction between cells on either side of this boundary, perhaps through a transmembrane receptor, might initiate apoptosis.


Manjon, C., et al.
Nat. Cell Biol.