Restricted expression of cdc25a in the tailbud is essential for formation of the zebrafish posterior body.
Restricted expression of cdc25a in the tailbud is essential for formation of the zebrafish posterior body.
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DOI：
10.1101/gad.233577.113
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发表时间：
2014-02-15
影响因子：
10.5
通讯作者：
Kimelman D
中科院分区：
文献类型：
--
作者：
Bouldin CM;Snelson CD;Farr GH 3rd;Kimelman D
脊椎动物的身体是由多能干细胞样的祖细胞群形成的，这些祖细胞向胚胎的后端提供新分化的细胞。本研究的体内分析表明，斑马鱼胚胎的后端通过调控有丝分裂因子Cdc25a的表达，增殖被区隔化。此外，胚胎发生过程中增殖的区隔化对身体伸展和肌肉细胞的命运都是至关重要的。这项研究揭示了脊椎动物胚胎中细胞周期的精确调控与多能分化之间意想不到的联系。脊椎动物的身体是由多能干细胞样的祖细胞群形成的，这些祖细胞逐渐向胚胎的最后端提供新分化的细胞。由于很难在体内分析细胞分裂，祖细胞群如何平衡增殖和其他细胞功能尚不清楚。在这里，我们发现在斑马鱼早期发育过程中，通过cdc25a的调控表达，增殖在胚胎的后端被区分开，cdc25a是有丝分裂进入的关键控制者。通过使用错误表达cdc25a的转基因细胞系，我们发现这种区隔化对后体的形成至关重要。当cdc25a错误表达时，几个必需的T-box转录因子异常表达，包括Spadetail/Tbx16，它特异性地阻止myoD转录的正常开始，导致异常的肌肉形成。我们的研究结果表明，早期胚胎发生时增殖的区隔化对于脊椎动物体的延伸和多能后祖细胞向肌肉细胞命运的分化至关重要。
The vertebrate body forms from a multipotent stem cell-like progenitor population that contributes newly differentiated cells to the posterior end of the embryo. Here, in vivo analyses show that proliferation is compartmentalized at the posterior end of the zebrafish embryo via regulated expression of mitotic factor Cdc25a. Furthermore, compartmentalization of proliferation during embryogenesis is critical to both body extension and muscle cell fate. This study reveals an unexpected link between precise regulation of the cell cycle and differentiation from multipotency in the vertebrate embryo. The vertebrate body forms from a multipotent stem cell-like progenitor population that progressively contributes newly differentiated cells to the most posterior end of the embryo. How the progenitor population balances proliferation and other cellular functions is unknown due to the difficulty of analyzing cell division in vivo. Here, we show that proliferation is compartmentalized at the posterior end of the embryo during early zebrafish development by the regulated expression of cdc25a, a key controller of mitotic entry. Through the use of a transgenic line that misexpresses cdc25a, we show that this compartmentalization is critical for the formation of the posterior body. Upon misexpression of cdc25a, several essential T-box transcription factors are abnormally expressed, including Spadetail/Tbx16, which specifically prevents the normal onset of myoD transcription, leading to aberrant muscle formation. Our results demonstrate that compartmentalization of proliferation during early embryogenesis is critical for both extension of the vertebrate body and differentiation of the multipotent posterior progenitor cells to the muscle cell fate.
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