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First published online December 9, 2005
doi: 10.1242/10.1242/jcs.02708
Research Article |
1 Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
2 Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland
3 Department of Biology, Swiss Federal Institute of Technology, 8057 Zurich, Switzerland
4 Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington DC, 20010, USA
* Author for correspondence (e-mail: mckay{at}codon.nih.gov)
Accepted 21 September 2005
CNS stem cells are best characterized by their ability to self-renew and to generate multiple differentiated derivatives, but the effect of mitogenic signals, such as fibroblast growth factor 2 (FGF2), on the positional identity of these cells is not well understood. Here, we report that bone morphogenetic protein 2 (BMP2) induces telencephalic CNS stem cells to fates characteristic of neural crest and choroid plexus mesenchyme, a cell type of undetermined lineage in rodents. This induction occurs both in dissociated cell culture and cortical explants of embryonic day 14.5 (E14.5) embryos, but only when cells have been exposed to FGF2. Neither EGF nor IGF1 can substitute for FGF2. An early step in this response is activation of ß-catenin, a mediator of Wnt activity. The CNS stem cells first undergo an epithelial-to-mesenchymal transition and subsequently differentiate to smooth-muscle and non-CNS glia cells. Similar responses are seen with stem cells from E14.5 cortex, E18.5 cortex and adult subventricular zone, but with a progressive shift toward gliogenesis that is characteristic of normal development. These data indicate that FGF2 confers competence for dorsalization independently of its mitogenic action. This rapid and efficient induction of dorsal fates may allow identification of positional identity effectors that are co-regulated by FGF2 and BMP2.
Key words: Forebrain, Neural stem cell, Cranial neural crest, Choroid plexus mesenchyme (CPm), Epithelial-mesenchymal transition (EMT), Snai1, Snai2
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