title: Wnt8a and Wnt3a cooperate in the axial stem cell niche to promote mammalian body axis extension.
abstract: BACKGROUND
  Vertebrate body axis extension occurs in a head-to-tail direction from a caudal progenitor zone that responds to interacting signals. Wnt/β-catenin signaling is critical for generation of paraxial mesoderm, somite formation, and maintenance of the axial stem cell pool. Body axis extension requires Wnt8a in lower vertebrates, but in mammals Wnt3a is required, although the anterior trunk develops in the absence of Wnt3a.
  
  
  RESULTS
  We examined mouse Wnt8a(-/-) and Wnt3a(-/-) single and double mutants to explore whether mammalian Wnt8a contributes to body axis extension and to determine whether a posterior growth function for Wnt8a is conserved throughout the vertebrate lineage. We find that caudal Wnt8a is expressed only during early somite stages and is required for normal development of the anterior trunk in the absence of Wnt3a. During this time, we show that Wnt8a and Wnt3a cooperate to maintain Fgf8 expression and prevent premature Sox2 up-regulation in the axial stem cell niche, critical for posterior growth. Similar to Fgf8, Wnt8a requires retinoic acid (RA) signaling to restrict its caudal expression boundary and possesses an upstream RA response element that binds RA receptors.
  
  
  CONCLUSIONS
  These findings provide new insight into interaction of caudal Wnt-FGF-RA signals required for body axis extension.
authors: Development, Aging, and Regeneration Program, Sanford-Burnham Medical Research Institute, La Jolla, California.
authors: Thomas J
authors: TJ
authors: Cunningham
authors: Development, Aging, and Regeneration Program, Sanford-Burnham Medical Research Institute, La Jolla, California.
authors: Sandeep
authors: S
authors: Kumar
authors: Cancer and Developmental Biology Laboratory, NCI-Frederick, National Institutes of Health, Frederick, Maryland.
authors: Terry P
authors: TP
authors: Yamaguchi
authors: Development, Aging, and Regeneration Program, Sanford-Burnham Medical Research Institute, La Jolla, California.
authors: Gregg
authors: G
authors: Duester
mesh_terms: D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics; D000429:Alcohol Oxidoreductases / Q000172:deficiency / Q000235:genetics; D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D017124:Conserved Sequence; D051524:Fibroblast Growth Factor 8 / Q000096:biosynthesis / Q000235:genetics; D054262:Gastrulation; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D018168:Receptors, Retinoic Acid / Q000502:physiology; D020218:Response Elements / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D019170:Somites / Q000254:growth & development / Q000378:metabolism; D055153:Stem Cell Niche / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D014714:Vertebrates / Q000196:embryology; D051153:Wnt Proteins; D060509:Wnt3A Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: C496457:Fgf8 protein, mouse; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D018168:Receptors, Retinoic Acid; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C108545:Uncx4.1 protein, mouse; D051153:Wnt Proteins; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; C507016:Wnt8a protein, mouse; D051524:Fibroblast Growth Factor 8; D014212:Tretinoin; D000429:Alcohol Oxidoreductases; C113992:trans-retinol dehydrogenase
keywords: Fgf8; Rdh10; Wnt3a; Wnt8a; body axis extension; mouse; retinoic acid; somitogenesis