Promotion of the development of enteric neurons and glia by neuropoietic cytokines: interactions with neurotrophin-3

Dev Biol. 1998 Jun 15;198(2):343-65.


Neurotrophin-3 (NT-3) is known to promote enteric neuronal and glial development. Ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) were investigated to test the hypothesis that the development of subsets of enteric neurons and/or glia is also affected by a neuropoietic cytokine, by itself, or together with NT-3. Crest-derived cells, immunoselected from the fetal rat gut (E14) with antibodies to p75NTR, were found by RT-PCR and immunocytochemistry (after culture) to express both alpha (CNTER alpha) and beta components (gp130 and LIFR beta) of the tripartite CNTF receptor. In situ, myenteric ganglia below the esophagus were CNTFR alpha-immunoreactive by E16-E18. In vitro, CNTF and LIF induced in crest-derived cells nuclear translocation of STAT3 (signal transducer and activator of transcription 3), a concentration-dependent increase in expression of neuronal or glial markers, and a decrease in expression of the precursor marker, nestin. LIFR beta was expressed by more cells than CNTFR alpha; therefore, although the factors were equipotent, the maximal effect of LIF > CNTF. The cytokines and NT-3 were additive in promoting neuronal but not glial development. Specifically, the development of neurons expressing NADPH-diaphorase activity (an early marker found in inhibitory motor neurons) was promoted by CNTF and NT-3. These observations support the idea that a ligand for the tripartite CNTF receptor complex plays a role in ENS development.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Ciliary Neurotrophic Factor
  • DNA-Binding Proteins / metabolism
  • Female
  • Growth Inhibitors / pharmacology
  • Interleukin-6*
  • Intestines / embryology*
  • Intestines / innervation*
  • Leukemia Inhibitory Factor
  • Lymphokines / pharmacology
  • NADPH Dehydrogenase / metabolism
  • Nerve Growth Factors / physiology*
  • Nerve Tissue Proteins / pharmacology
  • Neural Crest / cytology
  • Neuroglia / physiology*
  • Neurons / physiology*
  • Neurotrophin 3
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Nerve Growth Factor
  • STAT3 Transcription Factor
  • Trans-Activators / metabolism


  • Ciliary Neurotrophic Factor
  • DNA-Binding Proteins
  • Growth Inhibitors
  • Interleukin-6
  • Leukemia Inhibitory Factor
  • Lymphokines
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Neurotrophin 3
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Nerve Growth Factor
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • Trans-Activators
  • NADPH Dehydrogenase
  • Receptor Protein-Tyrosine Kinases