Role of Hand1/eHAND in the dorso-ventral patterning and interventricular septum formation in the embryonic heart
Role of Hand1/eHAND in the dorso-ventral patterning and interventricular septum formation in the embryonic heart
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DOI：
10.1128/mcb.24.11.4627-4635.2004
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发表时间：
2004-06-01
影响因子：
5.3
通讯作者：
Tanaka, M
中科院分区：
文献类型：
--
作者：
Togi, K;Kawamoto, T;Tanaka, M
，胚胎心脏背腹构型和室间隔形成的分子机制尚不清楚。为了研究Hand1/eHAND在心腔形成中的作用，我们建立了Hand1/eHAND敲入小鼠，其中Hand1/eHAND基因被置于MLC2V启动子的控制下。在Hand1/eHand敲入小鼠中，右室和左室外弯扩大得更明显。此外，没有室间沟或间隔的形成，尽管在分子上，Hand1/eHand敲入心脏有两个心室。然而，Hand1/eHAND的表达不影响脑室内曲、房室管和流出道的形态。此外，Hand1/eHAND在整个脑室的表达改变了Chisel、ANF和Hand2/DHand的表达模式，但不影响Tbx5的表达。相反，在高表达Hand1/eHAND的转基因胚胎中，室间隔在右室正常形成，但在交界区不形成。这些结果提示Hand1/eHAND参与了室壁的扩张，左右室交界区Hand1/eHAND的表达缺失可能是室间沟和室间隔正常形成的关键。此外，Hand1/eHAND不是一个指定左室肌细胞谱系的主控基因，但可能与其他基因一起控制背腹侧模式。
,Molecular mechanisms for the dorso-ventral patterning and interventricular septum formation in the embryonic heart are unknown. To investigate a role of Hand1/eHAND in cardiac chamber formation, we generated Hand1/eHAND knock-in mice where Hand1/eHAND cDNA was placed under the control of the MLC2V promoter. In Hand1/eHAND knock-in mice, the outer curvature of the right and left ventricles expanded more markedly. Moreover, there was no interventricular groove or septum formation, although molecularly, Hand1/eHAND knock-in hearts had two ventricles. However, the morphology of the inner curvature of the ventricles, the atrioventricular canal, and the outflow tract was not affected by Hand1/eHAND expression. Furthermore, expression of Hand1/eHAND in the whole ventricles altered the expression patterns of Chisel, ANF,, and Hand2/dHAND but did not affect Tbx5 expression. In contrast, the interventricular septum formed normally in transgenic embryos overexpressing Hand1/eHAND in the right ventricle but not in the boundary region. These results suggested that Hand1/eHAND is involved in expansion of the ventricular walls and that absence of Hand1/eHAND expression in the boundary region between the right and left ventricles may be critical in the proper formation of the interventricular groove and septum. Furthermore, Hand1/eHAND is not a master regulatory gene that specifies the left ventricle myocyte lineage but may control the dorso-ventral patterning in concert with additional genes.