Tbx1 is necessary for palatal elongation and elevation
Tbx1 is necessary for palatal elongation and elevation
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DOI：
10.1016/j.mod.2010.03.001
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发表时间：
2010-05-01
影响因子：
2.6
通讯作者：
Brown, Christopher
中科院分区：
文献类型：
--
作者：
Goudy, Steven;Law, Amy;Brown, Christopher
转录因子TBX 1是与DiGeorge/Velocardiofacial综合征相关的发育异常的关键介导因子。小鼠研究表明，Tbx 1剂量减少会导致咽弓、心血管和颅面发育缺陷。Tbx 1在心脏发育中的作用已被深入研究，然而，其在腭发育中的作用知之甚少。通过研究Tbx 1-/-小鼠，我们发现在腭伸长和升高的临界点处存在缺陷。我们通过测量腭架长度、增殖、凋亡、相关生长因子表达和腭融合测定的变化来确定Tbx 1-/-小鼠中的固有腭缺陷。Tbx 1-/-胚胎表现出腭裂，100%的腭裂升高失败，50%的腭-口腔融合异常。在Tbx 1-/-小鼠中，腭架长度减少，舌高度增加，表明腭升高和并置存在物理障碍。体外腭融合测定证明Tbx 1-/-腭架能够融合，但滚筒培养测定显示无效腭架不能延长。Tbx 1-/-腭架中透明质酸产量减少可能解释腭架升高失败。此外，在Tbx 1-/-腭中细胞增殖和凋亡受到干扰。在Tbx 1-/-腭架中检测到Fgf 8表达的急剧下降，提示Fgf 8在腭中依赖于Tbx 1 Fgf 10在Tbx 1-/-腭架和舌中也上调。这些数据证明Tbx 1是指导腭伸长和升高的关键转录因子，并且腭中的Fgf 8表达是Tbx 1依赖性的（C）2010爱思唯尔爱尔兰有限公司版权所有
The transcription factor TBX1 is a key mediator of developmental abnormalities associated with DiGeorge/Velocardiofacial Syndrome Studies in mice have demonstrated that decreased dosage of Tbx1 results in defects in pharyngeal arch, cardiovascular, and craniofacial development The role of Tbx1 in cardiac development has been intensely studied, however, its role in palatal development is poorly understood By studying the Tbx1-/- mice we found defects during the critical points of palate elongation and elevation. The intrinsic palate defects in the Tbx1-/- mice we're determined by measuring changes in palate shelf length, proliferation, apoptosis, expression of relevant growth factors, and in palate fusion assays. Tbx1-/- embryos exhibit cleft palate with failed palate elevation in 100% and abnormal palatal-oral fusions in 50% In the Tbx1-/- mice the palate shelf length was reduced and tongue height was greater, demonstrating a physical impediment to palate elevation and apposition. In vitro palate fusion assays demonstrate that Tbx1-/- palate shelves are capable of fusion but a roller culture assay showed that the null palatal shelves were unable to elongate Diminished hyaluronic acid production in the Tbx1-/- palate shelves may explain failed palate shelf elevation In addition, cell proliferation and apoptosis were perturbed in Tbx1-/- palates A sharp decrease of Fgf8 expression was detected in the Tbx1-/- palate shelves, suggesting that Fgf8 is dependent on Tbx1 in the palate Fgf10 is also up-regulated in the Tbx1-/- palate shelves and tongue These data demonstrate that Tbx1 is a critical transcription factor that guides palatal elongation and elevation and that Fgf8 expression in the palate is Tbx1-dependent (C) 2010 Elsevier Ireland Ltd All rights reserved