JNK signaling is responsible for cell death in GMR>Aß42 background.

<p>(A, A′) Misexpression of both P35 and <i>puc</i> along with Aß42 (GMR>Aß42+P35<i>+puc</i>) results in strong rescue of cell death as evident from (A′) dramatically reduced TUNEL positive cells. However, the rescue of the phenotype was not significantly stronger than with blocking JNK signaling pathway alone (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024361#pone-0024361-g005" target="_blank">Figure 5G′</a>). (B) Misexpression of Aß42 (GMR>Aß42) in pupal retina showing cell death as evident from TUNEL positive cells (red channel). Blocking simultaneously both caspase-dependent cell death and caspase-independent JNK signaling mediated cell death in pupal retina (GMR>Aß42+P35<i>+puc</i>) showed a strong rescue in (C, C′, C″) pupal retina and (D) adult eye as compared to (B) GMR>Aß42 pupal retina, (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024361#pone-0024361-g003" target="_blank">Figure 3D</a>) GMR>Aß42 adult eye. The cell death is detected by TUNEL staining (red channel), which is (C′, C″) restricted to the periphery of the pupal retina. Note that dying cells on the periphery of the pupal retina corresponds to the programmed cell death as seen in the wild-type pupal retina too <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024361#pone.0024361-Brachmann1" target="_blank">[25]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024361#pone.0024361-Lin1" target="_blank">[28]</a>. (E) Quantification of the number of dying cells in eye imaginal discs based on TUNEL staining in different genetic combinations. The frequency of cell death in wild-type eye imaginal disc served as a control. Note that blocking JNK signaling (GMR>Aß42+<i>puc</i>) or blocking JNK signaling along with caspase–dependent cell death (GMR>Aß42+P35+<i>puc</i>) exhibit strong rescue of the neurodegenerative phenotype of GMR>Aß42. This rescue is significant (**) as seen by calculation of P-values based on one-tailed <i>t</i>-test using Microsoft Excel 2007.