Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2

Mol Cell. 2000 Jan;5(1):35-47. doi: 10.1016/s1097-2765(00)80401-3.


The left-right (L-R) asymmetric expression of lefty2 and nodal is controlled by a left side-specific enhancer (ASE). The transcription factor FAST2, which can mediate signaling by TGF beta and activin, has now been identified as a protein that binds to a conserved sequence in ASE. These FAST2 binding sites were both essential and sufficient for L-R asymmetric gene expression. The Fast2 gene is bilaterally expressed when nodal and lefty2 are expressed on the left side. TGF beta and activin can activate the ASE activity in a FAST2-dependent manner, while Nodal can do so in the presence of an EGF-CFC protein. These results suggest that the asymmetric expression of lefty2 and nodal is induced by a left side-specific TGF beta-related factor, which is most likely Nodal itself.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Cloning, Molecular
  • Conserved Sequence
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Enhancer Elements, Genetic
  • Feedback
  • Forkhead Transcription Factors
  • Gene Expression Regulation*
  • Left-Right Determination Factors
  • Mice
  • Mice, Transgenic
  • Nodal Protein
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Transforming Growth Factor beta / genetics*
  • Xenopus laevis


  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxh1 protein, mouse
  • Left-Right Determination Factors
  • Nodal Protein
  • Nodal protein, mouse
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Transcription Factors
  • Transforming Growth Factor beta