Expression of retinoic acid-synthesizing and -metabolizing enzymes during nephrogenesis in the rat.
Vitamin A signaling through its active form retinoic acid (RA) plays a critical role during kidney development and vitamin A deficiency in the rat induces renal hypoplasia. Here, we describe the distribution of four enzymes of the RA synthetic pathway (aldehyde dehydrogenases ALDH1A1-3 and ALDH8A1) and two enzymes of the degradative pathway (CYP26A1 and CYP26B1) in the developing rat metanephros. We provide evidence that each enzyme displays a cell-type specific expression pattern that changes considerably in the course of renal organogenesis and nephron differentiation. ALDH1A2 expression was restricted to the cortical stroma cell population, whereas ALDH8A1 transcripts were present in emerging renal vesicles. CYP26A1 and CYP26B1 mRNAs were absent during this time. Following nephron induction, ALDH1A1 remained weakly expressed in the UB ends, but was highly expressed in the UB-connected tubule and in all differentiating tubular segments of the developing nephron. ALDH1A2 was strongly expressed in the visceral layer of the developing glomeruli, as well as in cortical collecting tubules. ALDH1A3 mRNAs were found in the developing papilla and ureter. During postnatal nephrogenesis, ALDH1A3 and ALDH8A1 were co-expressed in the ureteric bud ends. CYP26A1 and CYP26B1 were both expressed from E18.5 onwards in S-shaped bodies, in tubular and glomerular anlagen, respectively. On the last day of nephrogenesis in the rat, CYP26B1 expression extended to UB ends. Our results indicate that tubular and glomerular differentiation of the nephron relies upon precise control of the RA metabolic pathway.
Marlier
Arnaud
A
INSERM U574, Hôpital Necker-Enfants Malades, Tour Lavoisier, 6ème étage, 149, rue de Sèvres, 75743 Paris Cedex 15, France.
Gilbert
Thierry
T
D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D009399:Nephrons / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D038081:Organogenesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000072516:Retinoic Acid 4-Hydroxylase; D014212:Tretinoin / Q000378:metabolism*
D012333:RNA, Messenger; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C000607082:Cyp26b1 protein, rat; D000072516:Retinoic Acid 4-Hydroxylase; D000444:Aldehyde Dehydrogenase