Functions of TGF-betta2 and GDNF in the development of the mouse nervous system:evidence from double mutant mice
A major area of investigations in neuroscience is directed at understanding factors that participate in neuronal survival and death. Therefore they are good candidates to be responsible for different neurodegenerative diseases such as Alzheimer’s, and Parkinson’s diseases. Many recent advancements in our laboratory have revealed that growth factors acting in synergy can regulate neuronal survival much more effectively than individual factors alone. Impairment of neuronal survival is the cause of a considerable number of neurodegenerative diseases. TGF-β has been shown to act in synergy with neurotrophic factors, most strikingly in combination with GDNF. Since no information was available about the overall signifi cance of TGF-β/GDNF cooperation and/or synergism for nervous system development, the present study was undertaken to test the paradigm of the developmental requirement of growth factor synergism and cooperation. Double knockout mice that lack both TGF-β2 and GDNF were generated. Neuron populations analyzed included all those in which biological effects of either growth factor had been documented before. Finally, an understanding of the role of TGF-β/GDNF synergism in vivo through the analysis of the nervous system development of the corresponding double mutant mice can provide signifi cant basic and clinical insight into mechanisms that may lead to overcoming neuron loss and verify potential targets for neurological diseases.