GDNF family members and their receptors: expression and functions in two oligodendroglial cell lines representing distinct stages of oligodendroglial development.
Glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN), and persephin (PSP) constitute a subfamily of transforming growth factor-betas (TGF-betas) with prominent roles in the regulation of neuron survival and differentiation. Although numerous members of the TGF-beta superfamily are important regulators of glial cell functions in health and disease, it is unknown whether any member of the GDNF subfamily may have functions in normal or pathological glial cell performances. To begin to address this issue, we have studied expression and putative functions of GDNF, NTN, PSP, and their receptors in two cell lines representing models for oligodendrocyte progenitor cells (OLI-neu) and immature oligodendrocytes (OLN-93), respectively. RT-PCR analysis revealed expression of all three growth factor mRNAs in OLI-neu and OLN-93 cells. Expression was weak in OLI-neu cells, while both NTN and PSP mRNAs were strongly expressed in OLN-93 cells. Furthermore, OLI-neu and OLN-93 cells expressed transcripts encoding the GDNF receptors Ret and GFRalpha-1. The two splice variants for GFRalpha-2 were exclusively synthesized in OLI-neu cells. Similarly, primary O-2A progenitor cells and enriched mature oligodendrocytes expressed Ret, GFRalpha-1 and GFRalpha-2 mRNAs. Both GDNF and NTN stimulated DNA synthesis monitored by BrdU incorporation of OLI-neu cells in a dose-dependent fashion. Co-administration of TGF-beta significantly reduced this effect. Similarly, PDGF co-applied with GDNF or NTN down-regulated proliferation in OLI-neu cells. In contrast, OLN-93 cells did not respond to GDNF or NTN with increased incorporation of BrdU. Expression of GDNF, NTN, and their receptors and distinct effects in two model cell lines of oligodendrocyte development suggest that functions of members of the GDNF family and their receptors may not be restricted to neurons and may be implicated in oligodendrocyte development.
Strelau
J
J
Neuroanatomy, University of Heidelberg, Germany. un691js3@genius.embnet.dkfz-heidelberg.de
Unsicker
K
K
D000818:Animals; D001483:Base Sequence; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage; D004247:DNA / Q000096:biosynthesis; D029721:Drosophila Proteins; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051101:Neurturin; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D029721:Drosophila Proteins; C495039:GDNF protein, human; C494987:GFRA1 protein, human; C495040:Gdnf protein, mouse; C495041:Gdnf protein, rat; C494988:Gfra1 protein, mouse; C494989:Gfra1 protein, rat; C494992:Gfra2 protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; C495053:NRTN protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D051101:Neurturin; C495056:Nrtn protein, mouse; C495057:Nrtn protein, rat; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; C110758:persephin; C095477:platelet-derived growth factor AB; D016222:Fibroblast Growth Factor 2; D004247:DNA; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse; C495001:Ret protein, rat; D001973:Bromodeoxyuridine