Meteorin promotes the formation of GFAP-positive glia via activation of the Jak-STAT3 pathway.
Meteorin is an orphan ligand which has been previously reported to control neuritogenesis and angiogenesis, as well as gliogenesis. However, the precise function of this factor in CNS development and the underlying molecular mechanisms are poorly understood. Here, we demonstrate that meteorin is involved in GFAP-positive glial differentiation through activation of the Jak-STAT3 pathway, by using neurosphere and retinal explant culture systems. During embryonic brain development, meteorin is highly expressed in neural stem and radial glia cells of the ventricular zone and immature neurons outside the ventricular zone but its expression disappears spontaneously as development proceeds except in GFAP-positive astrocytes. In cultured neurospheres, meteorin activates STAT3, and in turn increases the transcriptional activity of GFAP by enhancing the binding of STAT3 to the promoter. By meteorin stimulation, differentiating neurospheres show increased numbers of GFAP-positive cells, but the effect is abrogated by a blockade of the Jak-STAT3 pathway using either a Jak inhibitor or STAT3 siRNA. Furthermore, we expand our findings to the retina, and show that meteorin increases GFAP expression in Müller glia. Together, our results suggest that meteorin promotes GFAP-positive glia formation by mediating the Jak-STAT3 signaling pathway during both cortical stem cell differentiation and retinal glia development.
Lee
Hye Shin
HS
Neurovascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 151-742, Korea.
Han
Jiyeon
J
Lee
Soon-Hee
SH
Park
Jeong Ae
JA
Kim
Kyu-Won
KW
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004622:Embryo, Mammalian; D005904:Glial Fibrillary Acidic Protein; D053612:Janus Kinases / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000473:pathology; D009924:Organ Culture Techniques; D016548:Prosencephalon / Q000196:embryology / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D012160:Retina / Q000473:pathology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C528900:glial fibrillary astrocytic protein, mouse; C502098:meteorin protein, mouse; D053612:Janus Kinases