Editors' ChoiceApoptosis

Getting Over Cell Death

Science's STKE  09 Nov 2004:
Vol. 2004, Issue 258, pp. tw403
DOI: 10.1126/stke.2582004tw403

Many developmental processes involve programmed cell death, or apoptosis, to control cell number and ensure normal size, shape, and pattern development of tissues. In contrast, other developing tissues induce apoptosis only when exposed to a stress condition. In Drosophila, very little apoptosis occurs in the developing wing disc. However, exposure to x-rays can induce substantial cell death in the larval wing. Despite this, adult flies emerge from the treatment with normal wing morphology, which indicates that mechanisms are in place to compensate for cell loss. Perez-Garijo et al. report that increased expression of the signaling molecules Wingless (Wg) and Decapentaplegic (Dpp) may contribute to this process. Drosophila were engineered to express the caspase inhibitor, p35, in the posterior (P) compartment of the wing disc to uncouple apoptosis initiation (from x-ray exposure) from cell death. Expression of p35 had no effect on normal wing development. However, after exposure to x-rays during the larval stage, adult wings were abnormal in shape and larger in size, exclusively in the P compartment that overexpressed p35. Increased expression of two major patterning determinants, Wg and DPP, was observed in the P compartment. The excess cell proliferation, observed in the background of inhibited cell death, suggests that tissues that have initiated apoptosis could compensate for cell loss by providing proliferative signals. In the absence of completed apoptosis, secreted Wg and Dpp could stimulate cell proliferation and also affect cells in neighboring compartments. Likewise, tumorigenesis may result in part from the initiation of the apoptotic pathway coupled with inhibition of cell death, producing abnormal signaling of factors that cause cell proliferation.

A. Perez-Garijo, F. A. Martin, G. Morata, Caspase inhibition during apoptosis causes abnormal signalling and developmental aberrations in Drosophila. Development 131, 5591-5598 (2004). [Abstract] [Full Text]