title: Noggin and chordin have distinct activities in promoting lineage commitment of mouse embryonic stem (ES) cells.
abstract: To examine the role of secreted signaling molecules and neurogenic genes in early development, we have developed a culture system for the controlled differentiation of mouse embryonic stem (ES) cells. In the current investigation, two of the earliest identified BMP antagonists/neural-inducing factors, noggin and chordin, were expressed in pluripotent mouse ES cells. Neurons were present as early as 24 h following transfection of ES cells with a pCS2/noggin expression plasmid, with differentiation peaking at 72 h. With neuronal differentiation, stem cell marker genes were down-regulated and neural determination genes expressed. Coculture experiments and exposure to noggin-conditioned medium produced similar neuronal differentiation of control ES cells, while addition of BMP-4 to noggin expressants strikingly inhibited neuronal differentiation. Transfection of ES cells with a pCS2/chordin expression vector or exposure to chordin-conditioned medium produced a more complex pattern of differentiation; ES cells formed neurons, mesenchymal cells as well as N-CAM-positive, nestin-positive neuroepithelial progenitors. These data suggest that, consistent with their different expression fields, noggin and chordin may play distinct roles in patterning the early mouse embryo.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, 4748 MSII Building, Ann Arbor, MI 48109-0616, USA.
authors.forename: Theresa E
authors.initials: TE
authors.lastname: Gratsch
authors.forename: K Sue
authors.initials: KS
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D001483:Base Sequence; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002352:Carrier Proteins; D002454:Cell Differentiation; D019070:Cell Lineage; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000166:cytology*; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000502:physiology*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D011506:Proteins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D000099176:Noggin Protein
chemical_list: D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D017931:DNA Primers; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D000099176:Noggin Protein; C525810:Bmp4 protein, mouse; C054234:chordin