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 TGFβ ligands, Derrière/GDF1 and Xnr1/Nodal, together with inhibitors such as Lefty and Coco/Cerl2, 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 TGFβ 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 Derrière, but not Xnr1, signaling. The inhibitory effect is conserved, as APOBEC2 blocks TGFβ 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 TGFβ signaling and plays a major role in development.
Vonica
Alin
A
Laboratory of Vertebrate Embryology, The Rockefeller University, 1230 York Ave., New York, NY 10065, USA. av2443@columbia.edu
Rosa
Alessandro
A
Arduini
Brigitte L
BL
Brivanlou
Ali H
AH
D000818:Animals; D019521:Body Patterning; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D047108:Embryonic Development; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D017393:RNA Editing; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism
C118849:GDF3 protein, Xenopus; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C512833:nodal1 protein, Xenopus; D004247:DNA; D003564:Cytidine Deaminase