Onset of CNTFRalpha expression and signal transduction during neurogenesis in chick sensory dorsal root ganglia.

Abstract The expression of ciliary neurotrophic factor receptor α (CNTFRα) was investigated in the developing chick dorsal root ganglion (DRG) using affinity-purified anti-CNTFRα antibodies. At thoracic levels, CNTFRα-immunoreactivity (CNTFRα-IR) was first observed at stage 19 (E3) in cells with neuronal morphology. CNTFRα-IR is restricted to the neuronal lineage in the DRG throughout development. CNTFRα expression precedes that of neuron-specific β tubulin, Hu antigen, and Q211 antigen, which are markers expressed in developing sensory neurons. [ 3 H]Thymidine-labeling studies showed the onset of CNTFRα expression during terminal mitosis of sensory neuron precursors, making CNTFRα the earliest known neuronal marker in the DRG. CNTFRα-mediated signal transduction was demonstrated in E7 and E11 DRG neuron cultures by CNTF-induced STAT3 phosphorylation. Although low ligand concentrations (5 p M ) elicit STAT3 phosphorylation in E7 and E11 DRG neurons, a survival response is only observed in neurons from E11 DRG. This implicates a complex readout mechanism downstream of STAT3 phosphorylation leading to different cellular responses that depend on the age of the DRG neuron. These results argue against a role of CNTFRα ligands in the control of early neuron survival but are compatible with other functions in neurogenesis and sensory neuron development.