Onset of CNTFR alpha expression and signal transduction during neurogenesis in chick sensory dorsal root ganglia

The expression of ciliary neurotrophic factor receptor alpha (CNTFR alpha) was investigated in the developing chick dorsal root ganglion (DRG) using affinity-purified anti-CNTFR alpha antibodies. At thoracic levels, CNTFR alpha-immunoreactivity (CNTFR alpha-IR) was first observed at stage 19 (E3) in cells with neuronal morphology. CNTFR alpha-IR is restricted to the neuronal lineage in the DRG throughout development. CNTFR alpha expression precedes that of neuron-specific beta tubulin, Hu antigen, and Q211 antigen, which are markers expressed in developing sensory neurons. [H-3]Thymidine-labeling studies showed the onset of CNTFR alpha expression during terminal mitosis of sensory neuron precursors, making CNTFR alpha the earliest known neuronal marker in the DRG. CNTFR alpha-mediated signal transduction was demonstrated in E7 and E11 DRG neuron cultures by CNTF-induced STAT3 phosphorylation, Although low ligand concentrations (5 pM) elicit STAT3 phosphorylation in E7 and Ell DRG neurons, a survival response is only observed in neurons from Ell 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 CNTFR alpha ligands in the control of early neuron survival but are compatible with other functions in neurogenesis and sensory neuron development. (C) 1997 Academic Press.