APOBEC2, a selective inhibitor of TGFβ signaling, regulates left-right axis specification during early embryogenesis.

The specification of left-right asymmetry is an evolutionarily conserved developmental process in vertebrates. The interplay between two TGF beta ligands, Derriere/GDF1 and Xnr1/Nodal, together with inhibitors such as Lefty and Coco/CerI2, have been shown to provide the signals that lead to the establishment of laterality. However, molecular events leading to and following these signals remain mostly unknown. We find that APOBEC2, a member of the cytidine deaminase family of DNA/RNA editing enzymes, is induced by TGF beta signaling, and that its activity is necessary to specify the left-right axis in Xenopus and zebrafish embryos. Surprisingly, we find that APOBEC2 selectively inhibits Derriere, but not Xnr1, signaling. The inhibitory effect is conserved, as APOBEC2 blocks TGF beta signaling, and promotes muscle differentiation, in a mammalian myoblastic cell line. This demonstrates for the first time that a putative RNA/DNA editing enzyme regulates TGF beta signaling and plays a major role in development. (C) 2010 Elsevier Inc. All rights reserved.