miR-203 regulates progenitor cell proliferation during adult zebrafish retina regeneration.

miR-203 regulates progenitor cell proliferation during adult zebrafish retina regeneration.
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DOI:
10.1016/j.ydbio.2014.05.005
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发表时间:
2014-08-15
影响因子:
2.7
通讯作者:
Patton, James G.
Patton, James G.
中科院分区:
生物学3区
文献类型:
--
作者:
Rajaram, Kamya;Harding, Rachel L.;Hyde, David R.;Patton, James G.

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斑马鱼视网膜损伤触发自发再生反应,该反应由<s:1>勒神经胶质细胞(MG)去分化和不对称细胞分裂引发,产生多能祖细胞。祖细胞的增殖对视网膜再生至关重要。Pax6b在祖细胞中的表达是其增殖所必需的,但其表达的确切调控尚不清楚。在这里,我们发现miR-203在增殖祖细胞的再生过程中被下调。升高的miR-203水平抑制祖细胞扩增,但不影响MG去分化或祖细胞生成。通过gfp报告基因检测和视网膜中功能的获得和丧失实验,我们发现必须抑制miR-203的表达才能允许pax6b的表达和随后的祖细胞增殖。
Damage of the zebrafish retina triggers a spontaneous regeneration response that is initiated by Müller Glia (MG) dedifferentiation and asymmetric cell division to produce multipotent progenitor cells. Subsequent expansion of the progenitor pool by proliferation is critical for retina regeneration. Pax6b expression in the progenitor cells is necessary for their proliferation, but exact regulation of its expression is unclear. Here, we show that miR-203 is downregulated during regeneration in proliferating progenitor cells. Elevated miR-203 levels inhibit progenitor cell expansion without affecting MG dedifferentiation or progenitor cell generation. Using GFP-reporter assays and gain and loss of function experiments in the retina, we show that miR-203 expression must be suppressed to allow pax6b expression and subsequent progenitor cell proliferation.
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