OBJECTIVE: To evaluate whether lack of Dicer during calvaria development would lead to dysmorphology of calvaria and suture closure in mice. MATERIALS AND METHODS: A conditional Dicer deficient under Osx promoter mouse was employed in this study. The 4- and 10-week-old conditional Dicer-deficient mice control littermates and Osx-cre transgenic mice were studied for calvarial bone morphology and suture closure. Dry skull, microcomputed tomography (μCT), histological and gene expression studies were investigated to evaluate the effect of Dicer deficiency on calvarial bone morphology and their related genes during calvaria development. RESULTS: The results elucidated that complete suture closure was observed in 10-week-old conditional Dicer-deficient mice while incomplete closure suture was observed in age-matched Osx-cre control mice. The μCT and histological sections demonstrated complete fusion of posterior frontal suture and dysmorphic calvarial bones in Dicer deficient mice compared to the ones in their littermates and age-matched Osx-cre control mice. Gene expression study demonstrated significantly increased expression of suture and calvarial bone-related genes, that is Tgf-beta family, Bmp3, Msx2, Alx4, Runx2 and Osx in Dicer-deficient mice during suture closure time. CONCLUSIONS: The results suggest mature miRNAs are important for suture closure and calvarial morphology during calvaria development.
OBJECTIVE: To evaluate whether lack of Dicer during calvaria development would lead to dysmorphology of calvaria and suture closure in mice. MATERIALS AND METHODS: A conditional Dicer deficient under Osx promoter mouse was employed in this study. The 4- and 10-week-old conditional Dicer-deficient mice control littermates and Osx-cre transgenic mice were studied for calvarial bone morphology and suture closure. Dry skull, microcomputed tomography (μCT), histological and gene expression studies were investigated to evaluate the effect of Dicer deficiency on calvarial bone morphology and their related genes during calvaria development. RESULTS: The results elucidated that complete suture closure was observed in 10-week-old conditional Dicer-deficient mice while incomplete closure suture was observed in age-matched Osx-cre control mice. The μCT and histological sections demonstrated complete fusion of posterior frontal suture and dysmorphic calvarial bones in Dicer deficient mice compared to the ones in their littermates and age-matched Osx-cre control mice. Gene expression study demonstrated significantly increased expression of suture and calvarial bone-related genes, that is Tgf-beta family, Bmp3, Msx2, Alx4, Runx2 and Osx in Dicer-deficient mice during suture closure time. CONCLUSIONS: The results suggest mature miRNAs are important for suture closure and calvarial morphology during calvaria development.
Authors: Emily Bernstein; Sang Yong Kim; Michelle A Carmell; Elizabeth P Murchison; Heather Alcorn; Mamie Z Li; Alea A Mills; Stephen J Elledge; Kathryn V Anderson; Gregory J Hannon Journal: Nat Genet Date: 2003-10-05 Impact factor: 38.330