Morphogenesis of myocardial trabeculae in the mouse embryo
Morphogenesis of myocardial trabeculae in the mouse embryo
复制标题
DOI：
10.1111/joa.12465
复制
发表时间：
2016-08-01
影响因子：
2.4
通讯作者：
Mohun, Timothy J.
中科院分区：
文献类型：
--
作者：
Captur, Gabriella;Wilson, Robert;Mohun, Timothy J.
胚胎心脏中小梁的形成和出生前的重塑是脊椎动物心脏发生的一个显著特征，但人们对其知之甚少。破坏小鼠小梁发育的突变通常是胚胎致死的，这证明了小梁的重要性，并且异常的小梁结构与几种人类心脏病理学相关。在这里，小梁结构在发展中的小鼠胚胎已被分析使用高分辨率episcopic显微镜（HREM）和三维（3D）建模。这项研究表明，在从妊娠中期到出生的所有阶段，心室小梁包括一个复杂的心肌束网。这样的安排挑战了传统的测量方法，并且基于分形算法的方法已被用于提供小梁复杂性的客观测量。小梁形成的程度，因为它的变化沿着长度的左，右心室已被量化，并发生的变化，从形成的四腔心脏，直到出生前不久已被映射。这种方法不仅可以测量3D模型视觉检查中明显的定性特征，还可以检测区分每个心室及其发育阶段的细微、一致和区域性差异。最后，结合HREM成像和分形分析已被应用于分析在胚胎心脏结构的变化，在遗传小鼠模型中，小梁是紊乱的。研究表明，Notch途径组分Mib 1（Mib 1（flox/flox）; cTnT-cre）的心肌缺失导致一系列复杂的异常，影响小梁和心脏的其他部分。
Formation of trabeculae in the embryonic heart and the remodelling that occurs prior to birth is a conspicuous, but poorly understood, feature of vertebrate cardiogenesis. Mutations disrupting trabecular development in the mouse are frequently embryonic lethal, testifying to the importance of the trabeculae, and aberrant trabecular structure is associated with several human cardiac pathologies. Here, trabecular architecture in the developing mouse embryo has been analysed using high-resolution episcopic microscopy (HREM) and three-dimensional (3D) modelling. This study shows that at all stages from mid-gestation to birth, the ventricular trabeculae comprise a complex meshwork of myocardial strands. Such an arrangement defies conventional methods of measurement, and an approach based upon fractal algorithms has been used to provide an objective measure of trabecular complexity. The extent of trabeculation as it changes along the length of left and right ventricles has been quantified, and the changes that occur from formation of the four-chambered heart until shortly before birth have been mapped. This approach not only measures qualitative features evident from visual inspection of 3D models, but also detects subtle, consistent and regionally localised differences that distinguish each ventricle and its developmental stage. Finally, the combination of HREM imaging and fractal analysis has been applied to analyse changes in embryonic heart structure in a genetic mouse model in which trabeculation is deranged. It is shown that myocardial deletion of the Notch pathway component Mib1 (Mib1(flox/flox); cTnT-cre) results in a complex array of abnormalities affecting trabeculae and other parts of the heart.