The mammalian ShcB and ShcC phosphotyrosine docking proteins function in the maturation of sensory and sympathetic neurons

Shc proteins possess SH2 and PTB domains and serve a scaffolding function i n signaling by a variety of receptor tyrosine kinases. There are three know n mammalian She genes, of which ShcB and ShcC are primarily expressed in th e nervous system. We have generated null mutations in ShcB and ShcC and hav e obtained mice lacking either ShcB or ShcC or both gene products. ShcB-def icient animals exhibit a loss of peptidergic and nonpeptidergic nociceptive sensory neurons, which is not enhanced by additional loss of ShcC. Mice la cking both ShcB and ShcC exhibit a significant loss of neurons within the s uperior cervical ganglia, which is not observed in either mutant alone. The results indicate that these She family members possess both unique and ove rlapping functions in regulating neural development and suggest physiologic al roles for ShcB/ShcC in TrkA signaling.