Onset of CNTFRalpha expression and signal transduction during neurogenesis in chick sensory dorsal root ganglia.
The expression of ciliary neurotrophic factor receptor alpha (CNTFRalpha) was investigated in the developing chick dorsal root ganglion (DRG) using affinity-purified anti-CNTFRalpha antibodies. At thoracic levels, CNTFRalpha-immunoreactivity (CNTFRalpha-IR) was first observed at stage 19 (E3) in cells with neuronal morphology. CNTFRalpha-IR is restricted to the neuronal lineage in the DRG throughout development. CNTFRalpha expression precedes that of neuron-specific beta tubulin, Hu antigen, and Q211 antigen, which are markers expressed in developing sensory neurons. [3H]Thymidine-labeling studies showed the onset of CNTFRalpha expression during terminal mitosis of sensory neuron precursors, making CNTFRalpha the earliest known neuronal marker in the DRG. CNTFRalpha-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 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 CNTFRalpha ligands in the control of early neuron survival but are compatible with other functions in neurogenesis and sensory neuron development.
Holst
A
A
Max-Planck-Institut für Hirnforschung, Deutschordenstrasse 46, Frankfurt, D-60528, Federal Republic of Germany.
Heller
S
S
Junghans
D
D
Geissen
M
M
Ernsberger
U
U
Rohrer
H
H
D000818:Animals; D000906:Antibodies; D002455:Cell Division; D002478:Cells, Cultured; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000378:metabolism; D005727:Ganglia, Spinal / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis* / Q000502:physiology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology*; D013234:Stem Cells / Q000502:physiology; D013936:Thymidine / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
D000906:Antibodies; D004268:DNA-Binding Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; C095578:growth promoting activity receptor; D020794:Receptor Protein-Tyrosine Kinases; D013936:Thymidine