Reiterative roles for FGF signaling in the establishment of size and proportion of the zebrafish heart.
Reiterative roles for FGF signaling in the establishment of size and proportion of the zebrafish heart.
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DOI：
10.1016/j.ydbio.2008.06.033
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发表时间：
2008-09-15
影响因子：
2.7
通讯作者：
Yelon, Deborah
中科院分区：
文献类型：
--
作者：
Marques, Sara R.;Lee, Yoonsung;Poss, Kenneth D.;Yelon, Deborah
发展一个职能机构需要确定其适当的规模，以及确定其各个组成部分的相对比例。在斑马鱼的心脏中，器官的大小和比例在很大程度上取决于它的两个主要腔室--脑室和心房--中的细胞数量。斑马鱼Fgf8突变体的心脏大小和心脏比例都受到影响。为了确定成纤维细胞生长因子信号何时以及如何影响这些特征，我们检测了时间控制的通路抑制的效果。在心脏节律过程中，成纤维细胞生长因子信号的减少抑制了心室肌和心房肌细胞的形成，对心肌细胞的影响更大。在心肌细胞分化开始后，成纤维细胞生长因子信号的减少仍可导致心室肌细胞的缺失。与成纤维细胞生长因子在时间上的两种截然不同的作用一致，我们发现，成纤维细胞生长因子信号的增加只在心脏分化开始之前诱导心肌细胞过剩。因此，在心脏特化过程中，成纤维细胞生长因子信号首先调节心脏大小和心腔比例，然后在分化开始后通过调节细胞数量来优化心脏比例。总之，我们的数据表明，单一的信号通路可以重复地作用于协调器官的大小和比例。
Development of a functional organ requires the establishment of its proper size as well as the establishment of the relative proportions of its individual components. In the zebrafish heart, organ size and proportion depend heavily on the number of cells in each of its two major chambers, the ventricle and the atrium. Heart size and chamber proportionality are both affected in zebrafish fgf8 mutants. To determine when and how FGF signaling influences these characteristics, we examined the effect of temporally controlled pathway inhibition. During cardiac specification, reduction of FGF signaling inhibits formation of both ventricular and atrial cardiomyocytes, with a stronger impact on ventricular cells. After cardiomyocyte differentiation begins, reduction of FGF signaling can still result in a deficiency of ventricular cardiomyocytes. Consistent with two temporally distinct roles for FGF, we find that increased FGF signaling induces a cardiomyocyte surplus only before cardiac differentiation begins. Thus, FGF signaling first regulates heart size and chamber proportionality during cardiac specification and later refines ventricular proportion by regulating cell number after the onset of differentiation. Together, our data demonstrate that a single signaling pathway can act reiteratively to coordinate organ size and proportion.
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