Non-antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re-differentiation

Paula V Monje, Sayuri Rendon, Gagani Athauda, Margaret Bates, Patrick Wood, Mary B Bunge

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The expression of myelination-associated genes (MGs) can be induced by cyclic adenosine monophosphate (cAMP) elevation in isolated Schwann cells (SCs). To further understand the effect of known SC mitogens in the regulation of SC differentiation, we studied the response of SCs isolated from adult nerves to combined cAMP, growth factors, including neuregulin, and serum. In adult SCs, the induction of MGs by cAMP coincided with the loss of genes expressed in non-myelin-forming SCs and with a change in cell morphology from a bipolar to an expanded epitheliallike shape. Prolonged treatment with high doses of cAMP-stimulating agents, as well as low cell density, was required for the induction of SC differentiation. Stimulation with serum, neuregulin alone, or other growth factors including PDGF, IGF and FGF, increased SC proliferation but did not induce the expression of MGs or the associated morphological change. Most importantly, when these factors were administered in combination with cAMP-stimulating agents, SC proliferation was synergistically increased without reducing the differentiating activity of cAMP. Even though the initiation of DNA synthesis and the induction of differentiation were mostly incompatible events in individual cells, SCs were able to differentiate under conditions that also supported active proliferation. Overall, the results indicate that in the absence of neurons, cAMP can trigger SC re-differentiation concurrently with, but independently of, growth factor signaling.

Original languageEnglish
Pages (from-to)947-961
Number of pages15
JournalGLIA
Volume57
Issue number9
DOIs
StatePublished - Sep 8 2009

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Schwann Cells
Cyclic AMP
Cell Differentiation
Neuregulins
Intercellular Signaling Peptides and Proteins
Genes
Cell Proliferation
Serum
Mitogens
Cell Count
Neurons

Keywords

  • Forskolin
  • Growth factors
  • Myelination
  • Neuregulin
  • Proliferation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Non-antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re-differentiation. / Monje, Paula V; Rendon, Sayuri; Athauda, Gagani; Bates, Margaret; Wood, Patrick; Bunge, Mary B.

In: GLIA, Vol. 57, No. 9, 08.09.2009, p. 947-961.

Research output: Contribution to journalArticle

Monje, Paula V ; Rendon, Sayuri ; Athauda, Gagani ; Bates, Margaret ; Wood, Patrick ; Bunge, Mary B. / Non-antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re-differentiation. In: GLIA. 2009 ; Vol. 57, No. 9. pp. 947-961.
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