Noggin and chordin have distinct activities in promoting lineage commitment of mouse embryonic stem (ES) cells

Dev Biol. 2002 May 1;245(1):83-94. doi: 10.1006/dbio.2002.0629.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / physiology
  • Carrier Proteins
  • Cell Differentiation
  • Cell Lineage*
  • Coculture Techniques
  • Culture Media, Conditioned
  • DNA Primers
  • Embryo, Mammalian / cytology*
  • Gene Expression Profiling
  • Glycoproteins / physiology*
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins*
  • Mice
  • Proteins / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / cytology*


  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Carrier Proteins
  • Culture Media, Conditioned
  • DNA Primers
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Proteins
  • noggin protein
  • chordin