Developing with lethal RA levels: genetic ablation ofRargcan restore the viability of mice lackingCyp26a1
| Autor: | Pierre Chambon, Suzan Abu-Abed, Martin Petkovich, Pascal Dollé, Caroline Wood, Daniel Metzger, Glenn MacLean |
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| Rok vydání: | 2003 |
| Předmět: |
Fetal Proteins
Tail Mesoderm Receptors Retinoic Acid Retinoic acid Tretinoin Biology Mice chemistry.chemical_compound CYP26A1 FGF8 Cytochrome P-450 Enzyme System Downregulation and upregulation medicine Animals Molecular Biology Genetics Retinoic acid receptor gamma Retinoic Acid 4-Hydroxylase Embryo Mammalian Cell biology medicine.anatomical_structure chemistry embryonic structures Genes Lethal Signal transduction T-Box Domain Proteins WNT3A Developmental Biology |
| Zdroj: | Development. 130:1449-1459 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.00357 |
| Popis: | We have previously reported that the retinoic acid (RA) catabolizing enzyme CYP26A1 plays an important role in protecting tail bud tissues from inappropriate exposure to RA generated in the adjacent trunk tissues by RALDH2, and that Cyp26a1-null animals exhibit spina bifida and caudal agenesis. We now show that, in the absence of Cyp26a1, retinoic acid receptor gamma (RARγ) mediates ectopic RA-signaling in the tail bud. We also show that activated RARγ results in downregulation ofWnt3a and Fgf8, which integrate highly conserved signaling pathways known for their role in specifying caudal morphogenesis. Ablation of the gene for RARγ (Rarg) rescues Cyp26a1-null mutant animals from caudal regression and embryonic lethality, thus demonstrating that CYP26A1 suppresses the RA-mediated downregulation of WNT3A and FGF8 signaling pathways by eliminating ectopic RA in gastrulating tail bud mesoderm. |
| Databáze: | OpenAIRE |
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