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Dev Biol. February 1, 2011; 350 (1): 13-23.

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

Vonica A , Rosa A , Arduini BL , Brivanlou AH .

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.

PubMed ID: 20880495
PMC ID: PMC3038383
Article link: Dev Biol.
Grant support: R01 HD032105 NICHD NIH HHS , R03 HD057334 NICHD NIH HHS , R03 HD057334-01A2 NICHD NIH HHS , R01 HD032105 NICHD NIH HHS , R03 HD057334 NICHD NIH HHS , R03 HD057334-01A2 NICHD NIH HHS

Genes referenced: apobec2 cda dand5 gdf1 gdf3 lefty mut myod1 nodal nodal1 odc1 pnma2 t

Morpholinos referenced: apobec2 MO1 apobec2 MO2

Amthor, 2007, Pubmed[+]

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