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

The left-right (L-R) asymmetric expression of lefty2 and nodal is controlle d by a left side-specific enhancer (ASE). The transcription factor FAST2, w hich 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 bindin g sites were both essential and sufficient for L-R asymmetric gene expressi on. The Fast2 gene is bilaterally expressed when nodal and lefty2 are expre ssed on the left side. TGF beta and activin can activate the ASE activity i n 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 leffy 2 and nodal is induced by a left side-specific TGF beta-related factor, whi ch is most likely Nodal itself.