Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly.
Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly.
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DOI：
10.7554/elife.21172
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发表时间：
2017-01-18
期刊：
影响因子：
7.7
通讯作者：
Yelon D
中科院分区：
文献类型：
--
作者：
Bloomekatz J;Singh R;Prall OW;Dunn AC;Vaughan M;Loo CS;Harvey RP;Yelon D
邻近组织在指导器官的形态发生中起着核心作用，与相邻的内胚层相互作用，控制了心肌细胞的培养基，该过程称为心脏融合。突变PDGFRA破坏了斑马鱼和小鼠的心脏管组件。 pDGFAA的异位表达的心脏前体干扰心脏融合PDGF信号传导的一种启发性作用。
doi：http：//dx.doi.org/10.7554/elife.21172.001
In the growing embryo, the heart initially develops in the form of a simple tube. Its outer layer is made up of muscular cells, called myocardial cells, that pump blood through the tube. Before the heart tube developments, two groups of myocardial cells exist – one on each side of the embryo. To assemble the heart, these two populations of cells must move as a group to the middle of the embryo, where they meet and merge through a process called cardiac fusion. This movement of心肌细胞朝着胚胎的中间，取决于与邻近的组织的相互作用，该组织如何指导心肌细胞的运动。
PDGF信号通路指导体内几种不同类型的细胞的运动，但它与此途径的早期阶段没有联系，这是一种称为血小板衍生的生长因子（PDGF）的分子。 a编码PDGF受体的基因在心脏管组件中的缺陷进一步检查。
Bloomekatz等人也观察到，在正常的胚胎中，与心肌细胞相邻的内胚层会产生PDGF最重要的是，这些知识可能导致识别和治疗先天性心脏病的新方法。
doi：http：//dx.doi.org/10.7554/elife.21172.002
Communication between neighboring tissues plays a central role in guiding organ morphogenesis. During heart tube assembly, interactions with the adjacent endoderm control the medial movement of cardiomyocytes, a process referred to as cardiac fusion. However, the molecular underpinnings of this endodermal-myocardial relationship remain unclear. Here, we show an essential role for platelet-derived growth factor receptor alpha (Pdgfra) in directing cardiac fusion. Mutation of pdgfra disrupts heart tube assembly in both zebrafish and mouse. Timelapse analysis of individual cardiomyocyte trajectories reveals misdirected cells in zebrafish pdgfra mutants, suggesting that PDGF signaling steers cardiomyocytes toward the midline during cardiac fusion. Intriguingly, the ligand pdgfaa is expressed in the endoderm medial to the pdgfra-expressing myocardial precursors. Ectopic expression of pdgfaa interferes with cardiac fusion, consistent with an instructive role for PDGF signaling. Together, these data uncover a novel mechanism through which endodermal-myocardial communication can guide the cell movements that initiate cardiac morphogenesis. DOI: http://dx.doi.org/10.7554/eLife.21172.001 In the growing embryo, the heart initially develops in the form of a simple tube. Its outer layer is made up of muscular cells, called myocardial cells, that pump blood through the tube. Before the heart tube develops, two groups of myocardial cells exist – one on each side of the embryo. To assemble the heart, these two populations of cells must move as a group to the middle of the embryo, where they meet and merge through a process called cardiac fusion. This movement of myocardial cells toward the middle of the embryo depends upon interactions with a neighboring tissue called the endoderm. How the endoderm directs the movement of the myocardial cells was not well understood. The PDGF signaling pathway guides the movement of several different types of cells in the body, but it had not been previously linked to the early stages of heart tube assembly. In this pathway, a molecule called platelet-derived growth factor (PDGF) binds to PDGF receptors that sit on the surface of cells. Using microscopy and genetic analysis to study zebrafish and mouse embryos, Bloomekatz et al. now show that embryos that carry mutations in a gene that encodes a PDGF receptor suffer from defects in heart tube assembly. Further examination of the mutant zebrafish embryos revealed that the myocardial cells were not properly directed toward the middle of the embryo. In fact, many of these cells appeared to move away from the midline. Bloomekatz et al. also observed that, in normal embryos, the endoderm cells that lie adjacent to the myocardial cells produce PDGF. Therefore, it appears that PDGF produced by the endoderm could interact with PDGF receptors on the myocardial cells to direct these cells toward the middle of the embryo. The next step will be to figure out how this signaling influences the machinery inside the myocardial cells that controls their movement. Ultimately, this knowledge could lead to new ways to identify and treat congenital heart diseases. DOI: http://dx.doi.org/10.7554/eLife.21172.002