Dynamic expression of neurotrophic factor receptors in postnatal spinal motoneurons and in mouse model of ALS

J Neurobiol. 2006 Jul;66(8):882-95. doi: 10.1002/neu.20269.


Neurotrophic factors support the survival of spinal motoneurons (MNs) and have been considered as strong candidates for treating motoneuron diseases. However, it is unclear if the right combination of neurotrophic factor receptors is present in postnatal spinal MNs. In this study, we show that the level of c-ret expression remains relatively stable in embryonic and postnatal spinal MNs. In contrast, the mRNA and protein of GFRalpha1 and -2 are progressively down-regulated in postnatal life. By 3 and 6 months of age, both receptors are barely detectable in spinal MNs. The down-regulation of GFRalpha1 appears accelerated in transgenic mice expressing mutant SOD1(G93A). Despite the progressive loss of GFRalpha1 and -2, phosphorylation of c-ret shows no detectable reduction on tyrosine residues or on serine 696. In addition to the GFRalpha subunits, expression of TrkB also shows a dynamic change. During embryogenesis, there is twice as much full-length TrkB as the truncated TrkB isoform. However, this ratio is reversed in postnatal spinal cord. Expression of the mutant SOD1(G93A) appears to have no effect on the TrkB receptor ratio. Taken together, our data indicate that the expression of neurotrophic factor receptors, GFRalpha1, -2, and TrkB, is not static, but undergoes dynamic changes in postnatal spinal MNs. These results provide insights into the use of neurotrophic factors as therapeutic agents for ALS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Cell Differentiation / genetics
  • Disease Models, Animal
  • Down-Regulation / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / genetics
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism
  • Humans
  • Mice
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Motor Neurons / cytology
  • Motor Neurons / metabolism*
  • Mutation / genetics
  • Nerve Growth Factors / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-ret / genetics
  • Proto-Oncogene Proteins c-ret / metabolism
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism*
  • Spinal Cord / cytology
  • Spinal Cord / growth & development*
  • Spinal Cord / metabolism*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1


  • Gfra1 protein, mouse
  • Gfra2 protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Nerve Growth Factors
  • Receptors, Nerve Growth Factor
  • SOD1 protein, human
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Proto-Oncogene Proteins c-ret
  • Receptor, trkB