Distinct functions for Aldh1 and Raldh2 in the control of ligand production for embryonic retinoid signaling pathways.
During vertebrate embryogenesis retinoic acid (RA) synthesis must be spatiotemporally regulated in order to appropriately stimulate various retinoid signaling pathways. Various forms of mammalian aldehyde dehydrogenase (ALDH) have been shown to oxidize the vitamin A precursor retinal to RA in vitro. Here we show that injection of Xenopus embryos with mRNAs for either mouse Aldh1 or mouse Raldh2 stimulates RA synthesis at low and high levels, respectively, while injection of human ALDH3 mRNA is unable to stimulate any detectable level of RA synthesis. This provides evidence that some members of the ALDH gene family can indeed perform RA synthesis in vivo. Whole-mount immunohistochemical analyses of mouse embryos indicate that ALDH1 and RALDH2 proteins are localized in distinct tissues. RALDH2 is detected at E7.5-E10.5 primarily in trunk tissue (paraxial mesoderm, somites, pericardium, midgut, mesonephros) plus transiently from E8.5-E9.5 in the ventral optic vesicle and surrounding frontonasal region. ALDH1 is first detected at E9.0-E10. 5 primarily in cranial tissues (ventral mesencephalon, dorsal retina, thymic primordia, otic vesicles) and in the mesonephros. As previous findings indicate that embryonic RA is more abundant in trunk rather than cranial tissues, our findings suggest that Raldh2 and Aldh1 control distinct retinoid signaling pathways by stimulating high and low RA biosynthetic activities, respectively, in various trunk and cranial tissues.
Haselbeck
R J
RJ
Gene Regulation Program, Burnham Institute, La Jolla, CA 92037, USA.
Hoffmann
I
I
Duester
G
G
D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D042931:Aldehyde Oxidase; D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000906:Antibodies; D004625:Embryo, Nonmammalian; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism; D050697:Retinal Dehydrogenase; D014212:Tretinoin / Q000378:metabolism*; D029867:Xenopus Proteins; D014982:Xenopus laevis
D000906:Antibodies; D007527:Isoenzymes; D012333:RNA, Messenger; D029867:Xenopus Proteins; D014212:Tretinoin; D000445:Aldehyde Oxidoreductases; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase; C493756:aldh1a2 protein, Xenopus; D042931:Aldehyde Oxidase