Atrioventricular valve development: new perspectives on an old theme.
Atrioventricular valve development: new perspectives on an old theme.
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DOI：
10.1016/j.diff.2012.04.001
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发表时间：
2012-07
期刊：
影响因子：
2.9
通讯作者：
Norris, Russell A.
中科院分区：
文献类型：
--
作者：
de Vlaming, Annemarieke;Sauls, Kimberly;Hajdu, Zoltan;Visconti, Richard P.;Mehesz, Agnes Nagy;Levine, Robert A.;Slaugenhaupt, Susan A.;Hagege, Albert;Chester, Adrian H.;Markwald, Roger R.;Norris, Russell A.
房室瓣的发育开始于EMT事件，其中内皮细胞转化为间充质细胞。诱导这种表型变化的分子事件是很好理解的，包括许多生长因子，信号传导成分和转录因子。除了它们在瓣膜发育中的明显重要性之外，这些转化的间充质的作用以及它们在瓣前小叶发育中的功能还鲜为人知。事实上，我们知道这些细胞会迁移，但它们是如何迁移的？为什么会迁移？我们还知道，它们经历向成熟的定向细胞的转变，由于它们分泌包括I型胶原蛋白在内的各种基质成分的能力，其主要被定义为间质成纤维细胞。然而，我们还没有发现基质合成的机制，它是如何分泌的，以及它是如何组织的。由于瓣膜疾病的主要特征是细胞数量改变、细胞活化和基质解体，因此回答瓣膜如何构建的问题可能会为我们提供真实的临床相关信息。虽然表达谱分析和描述性或相关性分析是有见地的，但为了推进该领域，我们现在必须超越这些测定的简单性，并提出基本的、基于机制的问题，旨在理解瓣膜是如何“构建”的。在此，我们回顾了目前对房室瓣发育的认识，并提出了什么是已知的，什么是未知的。在大多数情况下，几十年前提出的关于瓣膜发育的基本生物学问题和假设仍然有待回答，但可能是揭示与胚胎发育和成人心脏瓣膜疾病发育基础相关的新发现的关键。因此，本综述的目的是提醒我们这些问题，并就瓣膜开发的旧主题提供新的观点。
Atrioventricular valve development commences with an EMT event whereby endocardial cells transform into mesenchyme. The molecular events that induce this phenotypic change are well understood and include many growth factors, signaling components, and transcription factors. Besides their clear importance in valve development, the role of these transformed mesenchyme and the function they serve in the developing prevalve leaflets is less understood. Indeed, we know that these cells migrate, but how and why do they migrate? We also know that they undergo a transition to a mature, committed cell, largely defined as an interstitial fibroblast due to their ability to secrete various matrix components including collagen type I. However, we have yet to uncover mechanisms by which the matrix is synthesized, how it is secreted, and how it is organized. As valve disease is largely characterized by altered cell number, cell activation, and matrix disorganization, answering questions of how the valves are built will likely provide us with information of real clinical relevance. Although expression profiling and descriptive or correlative analyses are insightful, to advance the field, we must now move past the simplicity of these assays and ask fundamental, mechanistic based questions aimed at understanding how valves are ‘built”. Herein we review current understandings of atrioventricular valve development and present what is known and what isn’t known. In most cases, basic, biological questions and hypotheses that were presented decades ago on valve development still are yet to be answered but likely hold keys to uncovering new discoveries with relevance to both embryonic development and the developmental basis of adult heart valve diseases. Thus, the goal of this review is to remind us of these questions and provide new perspectives on an old theme of valve development.
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