Wnt signaling regulates the sequential onset of neurogenesis and gliogenesis via induction of BMPs.
In the mammalian central nervous system, neurogenesis precedes gliogenesis; neurons are primarily generated at the neural stage, whereas most glial cells are generated perinatally and postnatally. However, the signals that regulate this sequence of events remain unclear. Here we show that Wnt signaling induces neuronal and astroglial differentiation but suppresses oligodendroglial differentiation. We observed that precursor cells infected with a retrovirus encoding beta-catenin differentiated into neurons, while astrocytes developed from uninfected precursor cells surrounding infected cells. As neurogenesis proceeded, expression of the bone morphogenetic proteins (BMPs), BMP2, 4 and 7, progressively increased in the cells infected with the retrovirus encoding beta-catenin. Furthermore, treatment of cells with Noggin, a BMP antagonist, completely inhibited astroglial differentiation but partially restored oligodendroglial differentiation. These results suggest that Wnt signaling indirectly regulates gliogenesis by inducing BMPs in neuronal cells. Thus, cooperation between Wnt and BMP signaling may play a key role in determining the sequence of neurogenesis and gliogenesis.
Kasai
Mana
M
Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113, Japan.
Satoh
Kiyotoshi
K
Akiyama
Tetsu
T
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001921:Brain / Q000196:embryology; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009457:Neuroglia / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009836:Oligodendroglia / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse