In 1997, we have focussed on the role of HGF in development of sensory neurons. Anti-HGF antibodies also reduced the survival of neuroblasts but not sympathetic neurons. HGF greatly enhanced the neurite outgrowth and branching of NGF-dependent sympathetic neurons throughout development. These effects of anti-HGF antibodies and HGF were abolished by a disabling mutation of Met, the HGF receptor tyrosine kinase. The Met mutation also increased sympathetic neuroblast apoptosis in vivo.
Homozygous mutants show severe deficits in certain aspects of learning and memory.
Ras-GRF mutants do not learn to fear and avoid aversive stimuli in classical Pavlovian tasks that require the function of the amygdala. Electrophysiological measurements in the basolateral amygdala revealed that long-term plasticity was abnormal in mutant mice. In contrast, Ras-GRF mutants behave normally in spatial learning tasks like the Morris water maze, a test known to require hippocampal function. A role for the Ras signalling pathway in synaptic transmission and long-term memory. Nature 390, 281-286.