Fgfr3 expression by astrocytes and their precursors: evidence that astrocytes and oligodendrocytes originate in distinct neuroepithelial domains.
The postnatal central nervous system (CNS) contains many scattered cells that express fibroblast growth factor receptor 3 transcripts (Fgfr3). They first appear in the ventricular zone (VZ) of the embryonic spinal cord in mid-gestation and then distribute into both grey and white matter - suggesting that they are glial cells, not neurones. The Fgfr3(+) cells are interspersed with but distinct from platelet-derived growth factor receptor alpha (Pdgfra)-positive oligodendrocyte progenitors. This fits with the observation that Fgfr3 expression is preferentially excluded from the pMN domain of the ventral VZ where Pdgfra(+) oligodendrocyte progenitors--and motoneurones--originate. Many glial fibrillary acidic protein (Gfap)- positive astrocytes co-express Fgfr3 in vitro and in vivo. Fgfr3(+) cells within and outside the VZ also express the astroglial marker glutamine synthetase (Glns). We conclude that (1) Fgfr3 marks astrocytes and their neuroepithelial precursors in the developing CNS and (2) astrocytes and oligodendrocytes originate in complementary domains of the VZ. Production of astrocytes from cultured neuroepithelial cells is hedgehog independent, whereas oligodendrocyte development requires hedgehog signalling, adding further support to the idea that astrocytes and oligodendrocytes can develop independently. In addition, we found that mice with a targeted deletion in the Fgfr3 locus strongly upregulate Gfap in grey matter (protoplasmic) astrocytes, implying that signalling through Fgfr3 normally represses Gfap expression in vivo.
Pringle
Nigel P
NP
Wolfson Institute for Biomedical Research and Department of Biology, University College London, Gower Street, London WC1E 6BT, UK.
Yu
Wei-Ping
WP
Howell
Marisa
M
Colvin
Jennifer S
JS
Ornitz
David M
DM
Richardson
William D
WD
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology* / Q000196:embryology; D002642:Chick Embryo; D004848:Epithelium / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D011505:Protein-Tyrosine Kinases; D051381:Rats; D017207:Rats, Sprague-Dawley; D051498:Receptor, Fibroblast Growth Factor, Type 3; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D053823:Hedgehog Proteins; D017468:Receptors, Fibroblast Growth Factor; C465570:Shh protein, mouse; D015534:Trans-Activators; C496366:Fgfr3 protein, mouse; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D020796:Receptor, Platelet-Derived Growth Factor alpha; D005974:Glutamate-Ammonia Ligase