title: Inducible expression of noggin selectively expands neural progenitors in the adult SVZ.
abstract: Multipotent, self-renewing stem cells are present throughout the developing nervous system remaining in discrete regions of the adult brain. In the subventricular zone (SVZ) signaling molecules, including the bone morphogenetic proteins and their secreted inhibitor, noggin appear to play a critical role in controlling neural stem cell (NSC) behavior. To examine the function of this signaling pathway in the intact nervous system, we developed a transgenic mouse model in which noggin expression can be induced specifically in NSC via a nestin-driven reverse tetracycline-controlled transactivator (rtTA). In adult animals, the induction of noggin expression promotes the proliferation of neural progenitors in the SVZ, and shifts the differentiation of B cells (NSC) from mature astrocytes to transit amplifying C cells and oligodendrocyte precursor cells without depleting the NSC population. Noggin expression significantly increases neuronal and oligodendrocyte differentiation both in vivo and in vitro when NSCs are grown as neurospheres. These results demonstrate that noggin/BMP interactions tightly control cell fate in the SVZ.
authors.affiliation: Centro Pfizer de Genomica e Investigacion Oncologica, Universidad de Granada, Junta de Andalucia, Parque Tecnologico Ciencias de la Salud, Avda de la Ilustracion, 114 18007, Granada Spain.
authors.forename: M
authors.initials: M
authors.lastname: Morell
authors.affiliation: Department of Cell and Developmental Biology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Yao-chang
authors.initials: YC
authors.lastname: Tsan
authors.affiliation: Department of Cell and Developmental Biology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: oshea@umich.edu.
authors.forename: K Sue
authors.initials: KS
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D001253:Astrocytes; D019485:Bone Morphogenetic Proteins / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D007150:Immunohistochemistry; D020547:Lateral Ventricles / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D064231:Nestin / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D015398:Signal Transduction; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D064231:Nestin; D000099176:Noggin Protein