Fgf signaling instructs position-dependent growth rate during zebrafish fin regeneration

Fgf signaling instructs position-dependent growth rate during zebrafish fin regeneration
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DOI:
10.1242/dev.02101
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发表时间:
2005-12-01
期刊:
影响因子:
4.6
通讯作者:
Poss, KD
Poss, KD
中科院分区:
生物学2区
文献类型:
--
作者:
Lee, Y;Grill, S;Poss, KD

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在尾尾鱼和硬骨鱼的附属物再生过程中,组织的替换受到精确的调节,因此只有适当的结构才会被恢复,这种现象被称为位置记忆。人们认为,截肢后,在附属物的近端远端(PD)轴上存在或迅速建立一个动态的位置信息梯度,为受伤组织分配特定区域的指令。这些指令规定了再生组织的数量,以及再生生长发生的速度。在许多物种中,一个引人注目的主题是,与远端截肢相比,近端截肢的附属物再生速度更快。然而,潜在的分子调控尚不清楚。在这里,我们确定了斑马鱼尾鳍再生过程中生长速度的位置依赖性差异。这些生长速率与胚芽长度、有丝分裂指数和Fgf靶基因mkp3、sef和spry4的表达的位置依赖性差异有关。为了解决PD中Fgf信号量的差异是否与位置依赖性囊胚功能有关,我们已经产生了转基因鱼,其中Fgf受体活性可以通过实验来操纵。我们发现Fgf信号水平严格控制靶基因表达、胚细胞增殖和再生生长速度。我们的研究结果表明,Fgf信号决定了斑马鱼再生附属物的位置依赖性胚质特性和生长速率。
During appendage regeneration in urodeles and teleosts, tissue replacement is precisely regulated such that only the appropriate structures are recovered, a phenomenon referred to as positional memory. It is believed that there exists, or is quickly established after amputation, a dynamic gradient of positional information along the proximodistal (PD) axis of the appendage that assigns region-specific instructions to injured tissue. These instructions specify the amount of tissue to regenerate, as well as the rate at which regenerative growth is to occur. A striking theme among many species is that the rate of regeneration is more rapid in proximally amputated appendages compared with distal amputations. However, the underlying molecular regulation is unclear. Here, we identify position-dependent differences in the rate of growth during zebrafish caudal fin regeneration. These growth rates correlate with position-dependent differences in blastemal length, mitotic index and expression of the Fgf target genes mkp3, sef and spry4. To address whether PD differences in amounts of Fgf signaling are responsible for position-dependent blastemal function, we have generated transgenic fish in which Fgf receptor activity can be experimentally manipulated. We find that the level of Fgf signaling exhibits strict control over target gene expression, blastemal proliferation and regenerative growth rate. Our results demonstrate that Fgf signaling defines position-dependent blastemal properties and growth rates for the regenerating zebrafish appendage.