Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Genes Dev. 2014 Feb 15;28(4):384-95. doi: 10.1101/gad.233577.113. Epub 2014 Jan 29.
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.
脊椎动物的身体由多能干细胞样祖细胞群体形成,这些祖细胞群体逐渐将新分化的细胞贡献给胚胎的最尾端。由于难以在体内分析细胞分裂,祖细胞群体如何平衡增殖和其他细胞功能尚不清楚。在这里,我们通过调控 cdc25a 的表达,展示了在早期斑马鱼发育过程中,胚胎尾部的增殖是分区的,而 cdc25a 是有丝分裂进入的关键控制器。通过使用一个过表达 cdc25a 的转基因系,我们表明这种分区对于形成身体的尾部至关重要。在 cdc25a 过表达时,几个重要的 T 盒转录因子异常表达,包括 Spadetail/Tbx16,它特异性地阻止了 myoD 转录的正常开始,导致异常的肌肉形成。我们的结果表明,早期胚胎发生中增殖的分区对于脊椎动物身体的延伸以及多能尾部祖细胞分化为肌肉细胞命运都至关重要。