PMID:24045938

Citation	Kam, RK, Shi, W, Chan, SO, Chen, Y, Xu, G, Lau, CB, Fung, KP, Chan, WY and Zhao, H' (2013) dhrs3 attenuates retinoic acid signaling and is required for early embryonic patterning. J. Biol. Chem. '
Abstract	All-trans retinoic acid (atRA) is an important morphogen involved in many developmental processes, including neural differentiation, body axis formation, and organogenesis. During the early embryonic development, atRA is synthesized from all-trans retinal (atRAL) in an irreversible reaction mainly catalyzed by retinal dehydrogenase 2 (aldh1a2), while atRAL is converted from all-trans retinol (atROL) via reversible oxidation by retinol dehydrogenases (RDHs), members of the short-chain dehydrogenase/reductase (SDR) 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 showed 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 RA 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 through reducing atRAL levels, and is required for proper anteroposterior axis formation, neuroetoderm patterning, and somitogenesis.
Links	PubMed Online version:10.1074/jbc.M113.514984
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
XENTR:Q68ER5		GO:1900053: negative regulation of retinoic acid biosynthetic process	ECO:0000315:		P		Figure 4.	complete CACAO 8893
XENTR:Q68ER5		GO:0009948: anterior/posterior axis specification	ECO:0000315:		P		Figure 5 D,E and F	complete CACAO 8894
XENTR:Q68ER5		GO:1901232: regulation of convergent extension involved in axis elongation	ECO:0000315:		P		Figure 7	complete CACAO 8896
XENTR:Q68ER5		GO:0008078: mesodermal cell migration	ECO:0000315:		P		Figure 6	complete CACAO 8897
XENTR:Q68ER5		GO:0001756: somitogenesis	ECO:0000315:		P		Figure 8	complete CACAO 8898
XENLA:Q6GNT6	involved_in	GO:0009948: anterior/posterior axis specification	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
XENLA:Q6GNT6	involved_in	GO:0001756: somitogenesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
XENLA:Q6GNT6		GO:0001756: somitogenesis	ECO:0000315:		P		Figure 8	complete CACAO 9035
XENLA:Q6GNT6		GO:0008078: mesodermal cell migration	ECO:0000315:		P		Figure 6	complete CACAO 9036
XENLA:Q6GNT6		GO:0009948: anterior/posterior axis specification	ECO:0000315:		P		Figure 5 D	complete CACAO 9037
XENLA:Q6GNT6		GO:0010634: positive regulation of epithelial cell migration	ECO:0000315:		P		Figure 5A - Cdc42 overexpression showed MECs were significantly more migratory	complete CACAO 9038
XENLA:Q6GNT6		GO:1900053: negative regulation of retinoic acid biosynthetic process	ECO:0000314:		P		Figure 4	complete CACAO 9039
XENLA:Q6GNT6		GO:1901232: regulation of convergent extension involved in axis elongation	ECO:0000315:		P		Figure 7	complete CACAO 9040
XENLA:Q6GNT6	involved_in	GO:1900053: negative regulation of retinoic acid biosynthetic process	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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