title: Uncoupling of retinoic acid signaling from tailbud development before termination of body axis extension.
abstract: During the early stages of body axis extension, retinoic acid (RA) synthesized in somites by Raldh2 represses caudal fibroblast growth factor (FGF) signaling to limit the tailbud progenitor zone. Excessive RA down-regulates Fgf8 and triggers premature termination of body axis extension, suggesting that endogenous RA may function in normal termination of body axis extension. Here, we demonstrate that Raldh2-/- mouse embryos undergo normal down-regulation of tailbud Fgf8 expression and termination of body axis extension in the absence of RA. Interestingly, Raldh2 expression in wild-type tail somites and tailbud from E10.5 onwards does not result in RA activity monitored by retinoic acid response element (RARE)-lacZ. Treatment of wild-type tailbuds with physiological levels of RA or retinaldehyde induces RARE-lacZ activity, validating the sensitivity of RARE-lacZ and demonstrating that deficient RA synthesis in wild-type tail somites and tailbud is due to a lack of retinaldehyde synthesis. These studies demonstrate an early uncoupling of RA signaling from mouse tailbud development and show that termination of body axis extension occurs in the absence of RA signaling.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Cunningham
authors.forename: Xianling
authors.initials: X
authors.lastname: Zhao
authors.forename: Gregg
authors.initials: G
authors.lastname: Duester
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D007763:Lac Operon; D051379:Mice; D018345:Mice, Knockout; D020218:Response Elements / Q000187:drug effects; D012172:Retinaldehyde / Q000494:pharmacology; D015398:Signal Transduction; D019170:Somites / Q000187:drug effects / Q000378:metabolism; D013234:Stem Cells; D013623:Tail / Q000196:embryology*; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C496457:Fgf8 protein, mouse; D051524:Fibroblast Growth Factor 8; D014212:Tretinoin; D005346:Fibroblast Growth Factors; D000445:Aldehyde Oxidoreductases; C470579:RALDH2 protein, mouse; D012172:Retinaldehyde