Left–Right Asymmetric Expression of lefty2 and nodal Is Induced by a Signaling Pathway that Includes the Transcription Factor FAST2

Abstract

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 TGFβ 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. TGFβ 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 TGFβ-related factor, which is most likely Nodal itself.