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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chalazonitis, A; Rothman, TP; Chen, J; Vinson, EN; MacLennan, AJ; Gershon, MD

Published Date

  • June 15, 1998

Published In

Volume / Issue

  • 198 / 2

Start / End Page

  • 343 - 365

PubMed ID

  • 9659938

Pubmed Central ID

  • 9659938

International Standard Serial Number (ISSN)

  • 0012-1606

Language

  • eng

Conference Location

  • United States