How does Wingless promote wing disc cell
survival?
Our lab has recently shown that
Drosophila Wingless (Wg), a
key patterning morphogen, is required for
cell survival during wing development. The mechanism by which Wg
carries out this function is unknown. Cell death in Drosophila is
regulated by a well-defined pathway. We are exploring how Wg
promotes cell survival through the regulation of the genes in this
pathway. For example, Wg may directly or indirectly silence or
attenuate pro-apoptotic genes such as hid,
reaper or grim.
Conversely, Wg could promote survival by upregulating levels of
anti-apoptotic genes such as thread/diap1.
An alternative
possibility is suggested by the recent demonstration that
discontinuities in morphogen gradients, such as results when Wg
signaling is disrupted, can lead to activation of Jun N-terminal kinase
(JNK) signaling and to the death of cells, perhaps as a mechanism for
correcting mistakes in wing patterning. Thus Wg activity may
prevent activation of the stress-induced JNK pathway.
To determine how Wg specifically
controls cell survival, we are modulating Wg activity in small
populations of cells in the wing disc. We find that loss of Wg
activity results in increased cell death, increased proliferation and a
profound reduction of wing disc size during the third instar. We
are using a combination of genetics and molecular biology to understand
these observations and to define how Wg activity regulates cell
survival.