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

TY - JOUR

T1 - Onset of CNTFRalpha expression and signal transduction during neurogenesis in chick sensory dorsal root ganglia

AU - Holst, A

AU - Heller, S

AU - Junghans, D

AU - Geissen, M

AU - Ernsberger, U

AU - Rohrer, H

N1 - Copyright 1997 Academic Press.

PY - 1997/11/1

Y1 - 1997/11/1

N2 - 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.

AB - 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.

KW - Animals

KW - Antibodies

KW - Cell Division

KW - Cells, Cultured

KW - Chick Embryo

KW - DNA-Binding Proteins/metabolism

KW - Ganglia, Spinal/embryology

KW - Gene Expression Regulation, Developmental

KW - Immunohistochemistry

KW - Neurons/cytology

KW - Neurons, Afferent/cytology

KW - Phosphorylation

KW - Receptor Protein-Tyrosine Kinases/biosynthesis

KW - Receptor, Ciliary Neurotrophic Factor

KW - Receptors, Nerve Growth Factor/biosynthesis

KW - STAT3 Transcription Factor

KW - Signal Transduction

KW - Spinal Cord/cytology

KW - Stem Cells/physiology

KW - Thymidine/metabolism

KW - Trans-Activators/metabolism

U2 - 10.1006/dbio.1997.8714

DO - 10.1006/dbio.1997.8714

M3 - SCORING: Journal article

C2 - 9356167

VL - 191

SP - 1

EP - 13

JO - DEV BIOL

JF - DEV BIOL

SN - 0012-1606

IS - 1

ER -