کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2175496 1093842 2007 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dosage-dependent transcriptional regulation by the calcineurin/NFAT signaling in developing myocardium transition
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Dosage-dependent transcriptional regulation by the calcineurin/NFAT signaling in developing myocardium transition
چکیده انگلیسی

Thin spongy myocardium is critical at early embryonic stage [before embryonic day (E) 13.5 in mice] to allow diffusion of oxygen and nutrients to the developing cardiomyocytes. However, establishment of compact myocardium at later stage (∼ E16.5) during development is necessary to prepare for the increase in demand for blood circulation. Elucidating molecular targets of the spongy–compact myocardium transition between E13.5 and E16.5 in heart development is thus important. Previous studies demonstrated that multiple transcription factors and signaling pathways are involved in the regulation and function of the myocardium in heart development. Disruption of certain transcription factors or critical components of signaling pathways frequently causes structural malformation in heart and persistence of “thin spongy myocardium”. We have recently demonstrated activation of the calcineurin/NFAT signaling pathway at E14.5 in developing myocardium. Constitutive inhibition of the calcineurin/NFAT signaling pathway caused embryonic lethality. Molecular targets downstream of the calcineurin/NFAT signaling pathway, however, remains elusive. Here, we report transcription targets, independently and dependently, regulated by the calcineurin/NFAT signaling during the E13.5–E16.5 myocardium transition. We have uncovered that expression of one-third of the induced genes during myocardium transition is calcineurin/NFAT-dependent. Among these calcineurin/NFAT-dependent transcription targets, there is a dosage-dependent regulation. Molecular studies indicate that formation of distinct NFAT:DNA complex, in part, accounts for the dosage-dependent regulation. Thus, in addition to temporal and spatial regulation, dosage-dependent threshold requirement provides another mechanism to modulate transcription response mediated by the calcineurin/NFAT signaling during heart development.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Developmental Biology - Volume 303, Issue 2, 15 March 2007, Pages 825–837
نویسندگان
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