Growth/Differentiation Factor-5 (GDF-5) is a member of the Transforming Growth Factor-β superfamily (Storm et al. Nature368, 1994). It has been shown to be a potent neurotrophic factor in vitro(Krieglstein et al. J. Neurosci. Res. 42, 1995) and in vivo(Sullivan et al. Neurosci. Lett. 233, 1997) for rat dopaminergic midbrain neurones, those that degenerate in Parkinson's Disease. However there is no information on the role of GDF-5 in the normal brain. We have examined the expression of GDF-5 protein in the developing rat brain using embryos of E11 to E21 removed under terminal anaesthesia.
Western blotting of monoclonal antibody for GDF-5 revealed 2 immunoreactive bands at 56.8 kDa and 54.8 kDa. This agrees with the predicted size of the mouse monomeric GDF-5 precursor protein (preproGDF-5). In the rat dopaminergic neurones differentiate at around E12 and proliferate up to E15. We have found GDF-5 levels to be maximal at E15. The GDF-5 immunoreactive bands remain detectable throughout the developmental period. They are present in homogenates of rat ventral mesencephalon at E14 and E15, which contains developing midbrain dopaminergic neurones. Intense immunoreactivity was also found in the adult striatum and midbrain suggesting a possible role for this molecule in the maintenance of the adult nigrostriatal system. This is the first report detailing the expression of GDF-5 protein in the developing embyronic and adult rat brain. Its expression pattern matches the differentiation of dopaminergic neurones and the presence in the adult suggests that GDF-5 possibly provides support for dopaminergic neurones in vivo, lending support to the notion that GDF-5 could be used as a potential treatment for Parkinson's Disease.