Anzhi Chen1,2, Yanchao Han1,2,3, Kenneth D Poss1,2. 1. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA. 2. Regeneration Next, Duke University, Durham, North Carolina, USA. 3. Institute for Cardiovascular Science, Medical College, Soochow University, Suzhou, China.
Abstract
BACKGROUND: Vitamin D is an essential nutrient that has long been known to regulate skeletal growth and integrity. In models of major appendage regeneration, treatment with vitamin D analogs has been reported to improve aspects of zebrafish fin regeneration in specific disease or gene misexpression contexts, but also to disrupt pattern in regenerating salamander limbs. Recently, we reported strong mitogenic roles for vitamin D signaling in several zebrafish tissues throughout life stages, including epidermal cells and osteoblasts of adult fins. To our knowledge, molecular genetic approaches to dissect vitamin D function in appendage regeneration have not been described. RESULTS: Using a knock-in GFP reporter for the expression of the vitamin D target gene and negative regulator cyp24a1, we identified active vitamin D signaling in adult zebrafish fins during tissue homeostasis and regeneration. Transgenic expression of cyp24a1 or a dominant-negative vitamin D receptor (VDR) inhibited regeneration of amputated fins, whereas global vitamin D treatment accelerated regeneration. Using tissue regeneration enhancer elements, we found that local enhancement of VDR expression could improve regeneration with low doses of a vitamin D analog. CONCLUSIONS: Vitamin D signaling enhances the efficacy of fin regeneration in zebrafish.
BACKGROUND: Vitamin D is an essential nutrient that has long been known to regulate skeletal growth and integrity. In models of major appendage regeneration, treatment with vitamin D analogs has been reported to improve aspects of zebrafish fin regeneration in specific disease or gene misexpression contexts, but also to disrupt pattern in regenerating salamander limbs. Recently, we reported strong mitogenic roles for vitamin D signaling in several zebrafish tissues throughout life stages, including epidermal cells and osteoblasts of adult fins. To our knowledge, molecular genetic approaches to dissect vitamin D function in appendage regeneration have not been described. RESULTS: Using a knock-in GFP reporter for the expression of the vitamin D target gene and negative regulator cyp24a1, we identified active vitamin D signaling in adult zebrafish fins during tissue homeostasis and regeneration. Transgenic expression of cyp24a1 or a dominant-negative vitamin D receptor (VDR) inhibited regeneration of amputated fins, whereas global vitamin D treatment accelerated regeneration. Using tissue regeneration enhancer elements, we found that local enhancement of VDR expression could improve regeneration with low doses of a vitamin D analog. CONCLUSIONS: Vitamin D signaling enhances the efficacy of fin regeneration in zebrafish.
Authors: Andrew J Annalora; Ekaterina Bobrovnikov-Marjon; Rita Serda; Andrzej Pastuszyn; Sandra E Graham; Craig B Marcus; John L Omdahl Journal: Arch Biochem Biophys Date: 2006-12-03 Impact factor: 4.013
Authors: Wen-Yee Choi; Matthew Gemberling; Jinhu Wang; Jennifer E Holdway; Meng-Chieh Shen; Rolf O Karlstrom; Kenneth D Poss Journal: Development Date: 2013-02-01 Impact factor: 6.868
Authors: Mark R Haussler; Peter W Jurutka; Mathew Mizwicki; Anthony W Norman Journal: Best Pract Res Clin Endocrinol Metab Date: 2011-08 Impact factor: 4.690