کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10933108 1093767 2010 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeted deletion of the zebrafish obscurin A RhoGEF domain affects heart, skeletal muscle and brain development
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Targeted deletion of the zebrafish obscurin A RhoGEF domain affects heart, skeletal muscle and brain development
چکیده انگلیسی
Obscurin is a giant structural and signaling protein that participates in the assembly and structural integrity of striated myofibrils. Previous work has examined the physical interactions between obscurin and other cytoskeletal elements but its in vivo role in cell signaling, including the functions of its RhoGTPase Exchange Factor (RhoGEF) domain have not been characterized. In this study, morpholino antisense oligonucleotides were used to create an in-frame deletion of the active site of the obscurin A RhoGEF domain in order to examine its functions in zebrafish development. Cardiac myocytes in the morphant embryos lacked the intercalated disks that were present in controls by 72 and, in the more severely affected embryos, the contractile filaments were not organized into mature sarcomeres. Neural abnormalities included delay or loss of retinal lamination. Rescue of the phenotype with co-injection of mini-obscurin A expression constructs demonstrated that the observed effects were due to the loss of small GTPase activation by obscurin A. The immature phenotype of the cardiac myocytes and the retinal neuroblasts observed in the morphant embryos suggests that obscurin A-mediated small GTPase signaling promotes tissue-specific cellular differentiation. This is the first demonstration of the importance of the obscurin A-mediated RhoGEF signaling in vertebrate organogenesis and highlights the central role of obscurin A in striated muscle and neural development.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Developmental Biology - Volume 337, Issue 2, 15 January 2010, Pages 432-443
نویسندگان
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