Dhrs3 protein attenuates retinoic acid signaling and is required for early embryonic patterning.

Richard Kin Ting Kam, Weili Shi, Sun On Chan, Yonglong Chen, Gang Xu, Clara Bik-San Lau, Kwok Pui Fung, Wood Yee Chan, Hui Zhao

The Journal of biological chemistry 2013 Nov 01

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All-trans-retinoic acid (atRA) is an important morphogen involved in many developmental processes, including neural differentiation, body axis formation, and organogenesis. During early embryonic development, atRA is synthesized from all-trans-retinal (atRAL) in an irreversible reaction mainly catalyzed by retinal dehydrogenase 2 (aldh1a2), whereas atRAL is converted from all-trans-retinol via reversible oxidation by retinol dehydrogenases, members of the short-chain dehydrogenase/reductase family. atRA is degraded by cytochrome P450, family 26 (cyp26). We have previously identified a short-chain dehydrogenase/reductase 3 (dhrs3), which showed differential expression patterns in Xenopus embryos. We show here that the expression of dhrs3 was induced by atRA treatment and overexpression of Xenopus nodal related 1 (xnr1) in animal cap assay. Overexpression of dhrs3 enhanced the phenotype of excessive cyp26a1. In embryos overexpressing aldh1a2 or retinol dehydrogenase 10 (rdh10) in the presence of their respective substrates, Dhrs3 counteracted the action of Aldh1a2 or Rdh10, indicating that retinoic acid signaling is attenuated. Knockdown of Dhrs3 by antisense morpholino oligonucleotides resulted in a phenotype of shortened anteroposterior axis, reduced head structure, and perturbed somitogenesis, which were also found in embryos treated with an excess of atRA. Examination of the expression of brachyury, not, goosecoid, and papc indicated that convergent extension movement was defective in Dhrs3 morphants. Taken together, these studies suggest that dhrs3 participates in atRA metabolism by reducing atRAL levels and is required for proper anteroposterior axis formation, neuroectoderm patterning, and somitogenesis.

Citation

Richard Kin Ting Kam, Weili Shi, Sun On Chan, Yonglong Chen, Gang Xu, Clara Bik-San Lau, Kwok Pui Fung, Wood Yee Chan, Hui Zhao. Dhrs3 protein attenuates retinoic acid signaling and is required for early embryonic patterning. The Journal of biological chemistry. 2013 Nov 01;288(44):31477-87