TOWARDS A COMPREHENSIVE UNDERSTANDING OF THE TROPHIC SUPPORT OF MOTONEURONS

Motoneurons played an essential role in establishing the concept of ta rget-mediated support of innervating neurons. However, it took several decades until molecules were identified which trophically support mot oneurons in vitro and in vivo. The most potent molecule identified so far is ciliary neurotrophic factor (CNTF). It is expressed as a cytoso lic molecule in myelinating Schwann cells rather than in skeletal musc le in the postnatal period and therefore does not qualify as a target- derived neurotrophic factor regulating motoneuron survival during embr yonic development. However, the inactivation of CNTF by gene targeting experiments results in progressive atrophy and degeneration of motone urons, demonstrating that CNTF plays an essential role as a maintenanc e factor for motoneurons postnatally. Secretory molecules which are ex pressed in skeletal muscle during embryonic development and which supp ort motoneurons in culture and partially also in vivo include members of the NGF gene family (BDNF, NT-3, NT-4/5), FGF-5, IGF-1, and LIF. Th e evaluation of the physiological importance of these molecules is und er investigation.