Noggin antagonizes BMP signaling to create a niche for adult neurogenesis.
Large numbers of new neurons are born continuously in the adult subventricular zone (SVZ). The molecular niche of SVZ stem cells is poorly understood. Here, we show that the bone morphogenetic protein (BMP) antagonist Noggin is expressed by ependymal cells adjacent to the SVZ. SVZ cells were found to express BMPs as well as their cognate receptors. BMPs potently inhibited neurogenesis both in vitro and in vivo. BMP signaling cell-autonomously blocked the production of neurons by SVZ precursors by directing glial differentiation. Purified mouse Noggin protein promoted neurogenesis in vitro and inhibited glial cell differentiation. Ectopic Noggin promoted neuronal differentiation of SVZ cells grafted to the striatum. We thus propose that ependymal Noggin production creates a neurogenic environment in the adjacent SVZ by blocking endogenous BMP signaling.
Lim
D A
DA
Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Tramontin
A D
AD
Trevejo
J M
JM
Herrera
D G
DG
García-Verdugo
J M
JM
Alvarez-Buylla
A
A
D000818:Animals; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000494:pharmacology; D016380:Brain Tissue Transplantation; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D004805:Ependyma / Q000166:cytology / Q000378:metabolism; D016332:Fetal Tissue Transplantation; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008845:Microinjections; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D017978:Receptors, Growth Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000099176:Noggin Protein
D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D000099176:Noggin Protein