Embryological origins and development of the rat diaphragm
Embryological origins and development of the rat diaphragm
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DOI：
10.1002/cne.10503
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发表时间：
2003-01-20
影响因子：
2.5
通讯作者：
Greer, JJ
中科院分区：
文献类型：
--
作者：
Babiuk, RP;Zhang, W;Greer, JJ
胚胎学教科书提供了一套标准的图画和文字，反映了基于胚胎组织解剖学解剖的膈神经和膈肌发育的传统解释。在这里，我们重新审视这个问题，利用免疫组织化学标记的肌肉前体结合小鼠突变体进行系统的检查膈膈胚胎发生。这包括检查在肌发生的不同阶段膈神经轴突生长和肌肉前体的时空关系。此外，缺乏c-met受体的突变小鼠用于在不存在肌源性细胞的情况下可视化发育中的隔膜的间充质基质。我们没有发现任何证据表明横隔肌肉组织的贡献，从身体外侧壁，横隔，或食管间充质，作为标准的教条会状态。数据也不支持脚膈是不同的胚胎起源的假设。相反，我们发现肌源性细胞和轴突注定要形成膈肌的神经肌肉成分合并在胸膜腹膜褶皱（PPF）。正是PPF的这些组件的膨胀导致隔膜的形成。此外，我们将这些研究扩展到先天性膈疝（CDH）动物模型中检查隔膜的发育。我们发现PPF间充质基质的畸形导致CDH的缺陷特征。总之，数据表明，有必要对描述横膈膜正常和病理发育的叙述进行重大修改。
Textbooks of embryology provide a standard set of drawings and text reflecting the traditional interpretation of phrenic nerve and diaphragm development based on anatomical dissections of embryonic tissue. Here, we revisit this issue, taking advantage of immunohistochemical markers for muscle precursors in conjunction with mouse mutants to perform a systematic examination of phrenic-diaphragm embryogenesis. This includes examining the spatiotemporal relationship of phrenic axon outgrowth and muscle precursors during different stages of myogenesis. Additionally, mutant mice lacking c-met receptors were used to visualize the mesenchymal substratum of the developing diaphragm in the absence of myogenic cells. We found no evidence for contributions to the diaphragm musculature from the lateral body wall, septum transversum, or esophageal mesenchyme, as standard dogma would state. Nor did the data support the hypothesis that the crural diaphragm is of distinct embryological origins. Rather, we found that myogenic cells and axons destined to form the neuromuscular component of the diaphragm coalesce within the pleuroperitoneal fold (PPF). It is the expansion of these components of the PPF that leads to the formation of the diaphragm. Furthermore, we extended these studies to examine the developing diaphragm in an animal model of congenital diaphragmatic hernia (CDH). We find that malformation of the PPF mesenchymal substratum leads to the defect characteristic of CDH. In summary, the data demonstrates that a significant revision of narratives describing normal and pathological development of the diaphragm is warranted.