Motoneurons are lost in injured mice lacking Stat-3 (top) relative to wild type (bottom).

CNTF and related proteins have been shown to promote the survival of motoneurons in two different settings: during embryonic development and after nerve injury in adults. Because the signal and the response are apparently the same in the two situations, a simple explanation is that embryonic and adult neurons use the same signaling pathways to promote survival. But on page 287, Schweizer et al. show that the simplest hypothesis is not always the correct one.

Earlier work had shown that CNTF activates the LIF receptor to promote neuronal survival, and that Stat-3 is an important downstream effector of the LIF receptor. The authors used Cre-mediated recombination in a transgenic mouse system to delete the Stat-3 gene in neurons of the facial nucleus and spinal cord. Surprisingly, the mice develop normally, with no neuronal defects. When the facial nerves of adult mice are damaged, however, they show a dramatic loss of motoneurons compared with wild-type controls. Therefore, Stat-3–mediated signaling appears to be essential for motoneuron survival after injury, but dispensible during embryonic development, suggesting that neurons use different pathways at different times to transduce the same signal. ▪