Intracardiac septation requires hedgehog-dependent cellular contributions from outside the heart
Intracardiac septation requires hedgehog-dependent cellular contributions from outside the heart
复制标题
DOI：
10.1242/dev.016147
复制
发表时间：
2008-05-15
期刊：
影响因子：
4.6
通讯作者：
Klingensmith, John
中科院分区：
文献类型：
--
作者：
Goddeeris, Matthew M.;Rho, Silvia;Klingensmith, John
哺乳动物的心脏分割成四个腔室需要多个组织祖细胞的协调。这一过程的异常可导致潜在致命的房室分隔缺陷（AVSD）。心外细胞对房间隔的作用最近已被认识到。在这里，我们使用遗传标记和新的磁共振显微镜技术来证明背侧中心膜间质突出的起源，以及它对房室分隔的实质性贡献。我们通过研究先前未表征的Shh（-/-）突变小鼠胚胎的AVSD表型来探索该组织对房室分隔的功能意义。我们证明Shh信号在背侧心系膜内对心房的贡献是必需的。这种添加失败会导致严重的AVSD。这些研究表明，AVSD可能是由背侧中心膜原发缺陷引起的，为理解人类AVSD提供了新的范式。
Septation of the mammalian heart into four chambers requires the orchestration of multiple tissue progenitors. Abnormalities in this process can result in potentially fatal atrioventricular septation defects (AVSD). The contribution of extracardiac cells to atrial septation has recently been recognized. Here, we use a genetic marker and novel magnetic resonance microscopy techniques to demonstrate the origins of the dorsal mesenchymal protrusion in the dorsal mesocardium, and its substantial contribution to atrioventricular septation. We explore the functional significance of this tissue to atrioventricular septation through study of the previously uncharacterized AVSD phenotype of Shh(-/-) mutant mouse embryos. We demonstrate that Shh signaling is required within the dorsal mesocardium for its contribution to the atria. Failure of this addition results in severe AVSD. These studies demonstrate that AVSD can result from a primary defect in dorsal mesocardium, providing a new paradigm for the understanding of human AVSD.