Differential survival response of neurons to exogenous GDNF depends on the presence of skeletal muscle

Glial cell line-derived neurotrophic factor (GDNF) is known as a potent survival factor for neurons in vitro and in vivo. The current study investigated the effects of a single in utero injection with GDNF in both wild-type and Myf5-/-:MyoD-/- embryos. The embryos in the latter group, denoted double mutants (DM), do not contain skeletal muscle and associated neurotrophic factors due to lack of myogenesis and, therefore, neurons of the central and peripheral nervous system undergo excessively occurring programmed cell death (EPCD). We found that treatment with GDNF had no effect on wild type neuronal numbers in any of the anatomic locations investigated. However, GDNF rescued the neurons of the facial motor nucleus, the mesencephalic nucleus and the median motor column in the absence of skeletal muscle. The findings of the current study agree with previous reports that compromised mouse neurons have increased survival response to GDNF.