Decreased levels of embryonic retinoic acid synthesis accelerate recovery from arterial growth delay in a mouse model of DiGeorge syndrome.
نویسندگان
چکیده
RATIONALE Loss of Tbx1 and decrease of retinoic acid (RA) synthesis result in DiGeorge/velocardiofacial syndrome (DGS/VCFS)-like phenotypes in mouse models, including defects in septation of the outflow tract of the heart and anomalies of pharyngeal arch-derived structures including arteries of the head and neck, laryngeal-tracheal cartilage, and thymus/parathyroid. Wild-type levels of T-box transcription factor (Tbx)1 and RA signaling are required for normal pharyngeal arch artery development. Recent studies have shown that reduction of RA or loss of Tbx1 alters the contribution of second heart field (SHF) progenitor cells to the elongating heart tube. OBJECTIVE Here we tested whether Tbx1 and the RA signaling pathway interact during the deployment of the SHF and formation of the mature aortic arch. METHODS AND RESULTS Molecular markers of the SHF, neural crest and smooth muscle cells, were analyzed in Raldh2;Tbx1 compound heterozygous mutants. Our results revealed that the SHF and outflow tract develop normally in Raldh2(+/-);Tbx1(+/-) embryos. However, we found that decreased levels of RA accelerate the recovery from arterial growth delay observed in Tbx1(+/-) mutant embryos. This compensation coincides with the differentiation of smooth muscle cells in the 4th pharyngeal arch arteries, and is associated with severity of neural crest cell migration defects observed in these mutants. CONCLUSIONS Our data suggest that differences in levels of embryonic RA may contribute to the variability in great artery anomalies observed in DGS/VCFS patients.
منابع مشابه
Molecular Medicine Decreased Levels of Embryonic Retinoic Acid Synthesis Accelerate Recovery From Arterial Growth Delay in a Mouse Model of DiGeorge Syndrome
Rationale: Loss of Tbx1 and decrease of retinoic acid (RA) synthesis result in DiGeorge/velocardiofacial syndrome (DGS/VCFS)-like phenotypes in mouse models, including defects in septation of the outflow tract of the heart and anomalies of pharyngeal arch– derived structures including arteries of the head and neck, laryngeal–tracheal cartilage, and thymus/parathyroid. Wild-type levels of T-box ...
متن کاملThe effect of Fibroblast Growth Factor-2(FGF-2) and retinoic acid on differentiation of mouse embryonic stem cells into neural cells
Introduction: Embryonic Stem (ES) cells as pluripotent cells derived from the inner cell mass of blastula can differentiate to neural cells in vitro and this property is valuable in studies of neurogenesis and in the generation of donor cells for transplantation. In this regard, the propose of this research, was the study of the role of two important factors in the development of neural syst...
متن کاملThe Effect of Astrocyte-Conditioned Medium (ACM) and Retinoic Acid on Neural Differentiation of Mouse Embryonic Stem Cells
Purpose: The aim of this research was to study the properties of factors secreted from astrocyte cells in suspension medium in direct differentiation of mouse embryonic stem cells into neural cells. Materials and Methods: Royan B1 mouse embryonic stem (ES) cells were used in this experiment. For differentiation of Es cells into the neural cells, the astrocyte-condition medium (ACM) of mouse fe...
متن کاملDecreased embryonic retinoic acid synthesis results in a DiGeorge syndrome phenotype in newborn mice.
Retinoic acid (RA), the active derivative of vitamin A, is involved in various developmental and homeostatic processes. To define whether certain developmental events are particularly sensitive to a decrease in embryonic RA levels, we generated mice bearing a hypomorphic allele of the RA-synthesizing enzyme Raldh2. The resulting mutant mice, which die perinatally, exhibit the features of the hu...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Circulation research
دوره 106 4 شماره
صفحات -
تاریخ انتشار 2010