Role of TBX20 in endocardial cushion formation during chick heart development

TBX20 在鸡心脏发育过程中心内膜垫形成中的作用

• 批准号: 15590170
• 负责人: YAMAGISHI Toshiyuki
• 金额: $ 2.3万
• 依托单位: Saitama medical school
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590170/
• 关键词: heart development; cushion tissue; TBX20; chick embryo; 心房発生; TBX

The T-box gene family, which contains a DNA-binding domain of about 200 amino acids (T-box), is a new member of transcription factors. T-box genes thought to be concerned with many developmental processes. We have isolated a Tbx20 gene from chick embryo and found its strong expression in the embryonic heart. In situ hybridization showed that Tbx20 gene expressed in the precardiac mesoderm, and thereafter, in the looped heart, its transcripts were localized in the outflow tract (OT), bulbus cordis, atrioventricular (AV) canal and atrium. Moreover Tbx20 gene expressed strongly in the endocardial cushion tissue of OT and AV regions. Results suggest that Tbx20 gene may play an imporatant role in the cardiogenesis. And Tbx2,-5 and -20 were expressed during atrium development. Developmental anatomy shows that right and left atrium are developed from the sinus venosus, primitive atrium and dorsal mesocardium via the sequential embryonic processes such as, incorporation of the sinus venosus to the atrium, atrial septation and pulmonary venous development. However, mechanisms regulating these processes remain unknown. We examined expression patterns of Tbx2,-5,-20 in the developing atrium from stage 14 to 27 by in situ hybridization. Results suggest that differentially expressed Tbx2,-5,-20 may play an important role in the atrial development, such as septation and pulmonary venous development. Then, to determine whether Tbx20 is necessary for cushion tissue formation, we constructed Tbx20-engrailed2 (dominant negative form to Tbx20) and transfected into AV explants of stage 13 hearts on collagen gel lattice. Results indicated that Tbx20-engrailed2 inhibited endothelial to mesencymal transformation in vitro. These results suggested that Tbx20 may play a important role in cushion tissue formation during chick heart development.

T-box基因家族是转录因子的新成员，包含约200个氨基酸的dna结合域（T-box）。T-box基因被认为与许多发育过程有关。从鸡胚中分离出Tbx20基因，发现其在胚胎心脏中有较强的表达。原位杂交表明，Tbx20基因在心前中胚层表达，随后在环状心脏中，其转录本定位于流出道（OT）、心球、房室（AV）管和心房。Tbx20基因在OT和AV区的心内膜缓冲组织中表达强烈。结果提示Tbx20基因可能在心脏发生中起重要作用。Tbx2、-5、-20在心房发育过程中表达。发育解剖学表明，左、右心房由静脉窦、原始心房和心背系膜发育而来，经过静脉窦与心房合并、房间隔和肺静脉发育等一系列胚胎发育过程。然而，调节这些过程的机制仍然未知。我们通过原位杂交检测了Tbx2，-5，-20在14 - 27期发育中的心房中的表达模式。结果提示Tbx2、-5、-20的差异表达可能在心房分隔、肺静脉发育等发育过程中发挥重要作用。然后，为了确定Tbx20是否为缓冲组织形成所必需，我们构建了Tbx20- engred2 （Tbx20的显性阴性形式），并在胶原凝胶晶格上转染到13期心脏的AV外植体中。结果表明，Tbx20-engrailed2在体外抑制内皮细胞向间质转化。这些结果表明Tbx20可能在雏鸡心脏发育过程中缓冲组织的形成中起重要作用。

项目成果

Expression of tbx20 RNA during chick heart development

• DOI: 10.1002/dvdy.20076
• 发表时间: 2004-07
• 期刊: Developmental Dynamics
• 影响因子: 2.5
• 作者: T. Yamagishi;Y. Nakajima;S. Nishimatsu;T. Nohno;Katsumi Ando;Hiroaki Nakamura

Msx1 expression during chick heart development : possible role in endothelial-mesenchymal transformation during cushion tissue formation.

鸡心脏发育过程中的 Msx1 表达：缓冲组织形成过程中内皮间质转化的可能作用。

• 发表时间: 2005
• 期刊: Cardiovascular development and congenital malformations : Molecular and genetic mechanisms.(M.Artman, DW.Benson, D.Srivastava, M.Nakazawa (eds.)) (Futura Blackwell.Mass.)
• 作者: Yamagishi T.

Cardiovascular Development and Congenital Malformations. Molecular and genetic mechanisms

心血管发育和先天畸形。

• 发表时间: 2005
• 作者: Kokubo H;Miyagawa-Tomita S;et al.;Watanabe Noriko;中川 雅生;Hanato Takashi
• 通讯作者: Hanato Takashi