Identification of HGF-like protein as a novel neurotrophic factor for avian dorsal root ganglion sensory neurons

Abstract

HGF-like protein (HLP) is a member of the hepatocyte growth factor (HGF) family. Although HGF is shown to have neurotrophic activities on many of CNS and PNS neurons, the role of HLP in the nervous system is poorly understood despite the knowledge that Ron/HLP receptor is expressed in embryonic neurons. Here we show that HGF but not HLP promotes neurite extension and migration emanating from chick embryonic day 9 (E9) dorsal root ganglia (DRG) explants in the presence of low levels of NGF, however, HLP does promote neurite extension and cellular migration from E15 chick DRG explants with low levels of NGF. Ron-Fc, a chimeric molecule composed of the extracellular domain of Ron fused with immunoglobulin Fc, eliminated activities of HLP, such as cellular migration and long neurite extension emanating from E15 DRG explants in the presence of NGF, but did not eliminate short neurites. These results suggested that promotion of long neurite extension and migration depends on activities of HLP through its receptor/Ron. Taken together, we propose that HLP may play an important role in chick sensory ganglia at relatively late stages of development. This is the first evidence that HLP functions as a neurotrophic factor.