کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2173246 1093706 2012 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vivo knockdown of Brachyury results in skeletal defects and urorectal malformations resembling caudal regression syndrome
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
In vivo knockdown of Brachyury results in skeletal defects and urorectal malformations resembling caudal regression syndrome
چکیده انگلیسی

The T-box transcription factor BRACHYURY (T) is a key regulator of mesoderm formation during early development. Complete loss of T has been shown to lead to embryonic lethality around E10.0. Here we characterize an inducible miRNA-based in vivo knockdown mouse model of T, termed KD3-T, which exhibits a hypomorphic phenotype. KD3-T embryos display axial skeletal defects caused by apoptosis of paraxial mesoderm, which is accompanied by urorectal malformations resembling the murine uro-recto-caudal syndrome and human caudal regression syndrome phenotypes. We show that there is a reduction of T in the notochord of KD3-T embryos which results in impaired notochord differentiation and its subsequent loss, whereas levels of T in the tailbud are sufficient for axis extension and patterning. Furthermore, the notochord in KD3-T embryos adopts a neural character and loses its ability to act as a signaling center. Since KD3-T animals survive until birth, they are useful for examining later roles for T in the development of urorectal tissues.


► KD3-T is an in vivo knockdown model of Brachyury with a hypomorphic phenotype.
► The model has axial skeletal defects, a tail filament, and urorectal malformations.
► Remaining T protein in the notochord is insufficient to maintain its structure.
► T in the tailbud is functionally sufficient for axis extension.
► KD3-T provides a robust model for analyzing the Caudal Regression Syndrome.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Developmental Biology - Volume 372, Issue 1, 1 December 2012, Pages 55–67
نویسندگان
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