Glial cell line-derived neurotrophic factor promotes the development of adrenergic neurons in mouse neural crest cultures

Gerald D. Maxwell, Kate Reid, Andrew Elefanty, Perry F. Bartlett, Mark Murphy

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Abstract

Growth of mouse neural crest cultures in the presence of glial cell line-derived neurotrophic factor (GDNF) resulted in a dramatic dose-dependent increase in the number of tyrosine hydroxylase (TH)-positive cells that developed when 5% chicken embryo extract was present in the medium. In contrast, growth in the presence of bone morphogenetic protein (BMP)-2, BMP- 4, BMP-6, transforming growth factor (TGF) β1, TGF-β2, and TGF-β3 elicited no increase in the number of TH-positive cells. The TH-positive cells that developed in the presence of GDNF had neuronal morphology and contained the middle and low molecular weight neurofilament proteins. Numerous TH-negative cells with the morphology of neurons also were observed in GDNF-treated cultures. Analysis revealed that the period from 6 to 12 days in vitro was the critical time for exposure to GDNF to generate the increase in TH- positive cell number. The growth factors neurotrophin-3 and fibroblast growth factor-2 elicited increases in the number of TH-positive cells similar to that seen in response to GDNF. In contrast, nerve growth factor was unable to substitute for GDNF. These findings extend the previously reported biological activities of GDNF by showing that it can act on mouse neural crest cultures to promote the development of neurons.

Original languageEnglish
Pages (from-to)13274-13279
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number23
DOIs
Publication statusPublished - 12 Nov 1996
Externally publishedYes

Keywords

  • adrenergic development
  • neurogenesis
  • transforming growth factor β superfamily
  • tyrosine hydroxylase

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