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cdx4突变体未能指定血液祖先,并且可以通过多个假基因获救
Alan J Davidson1, Patricia Ernst, Yuan Wang
1Department of Medicine, Division of Hematology/Oncology, Children's Hospital and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
Nature
|September 19, 2003
概括
斑马鱼基因cdx4对于血液细胞发育和胚胎模式至关重要. cdx4中的突变通过改变霍克斯基因表达来破坏造血干细胞的形成,突出其在脊椎动物胚胎发生中的作用.
科学领域:
- 发育生物学是发展生物学.
- 遗传学 是一个遗传学.
- 血液形成 血液形成 血液形成
背景情况:
- 机体生成依赖于细胞类型的分化.
- 霍克斯基因沿前后轴建立位置性身份.
- 斑马鱼突变提供了研究发育缺陷的模型.
研究的目的:
- 确定负责斑马鱼突变kugelig (kgg) 的基因.
- 调查cdx4在造血和前后部造血模式中的作用.
- 阐明cdx4,霍克斯基因和血细胞命运规范之间的关系.
主要方法:
- 斑马鱼的基因选用于识别突变动物.
- 基因表达分析 (假基因).
- 涉及过度基因表达 (hoxb7a,hoxa9a,hoxb8a,scl,cdx4) 的救援实验.
- 小鼠胚胎干细胞研究.
主要成果:
- 这种kgg突变是由尾部相关基因cdx4.4中存在的缺陷引起的.
- kgg突变体表现出早期的造血缺陷和异常的前后图案与改变的霍克斯基因表达.
- 过度表达特定的hox基因 (hoxb7a,hoxa9a) 挽救了kgg胚胎的血液缺陷.
- cdx4过度表达诱导了斑马鱼和小鼠胚胎干细胞的血液形成和调节的HOX基因表达.
结论:
- cdx4 调节霍克斯基因表达.
- cdx4对于在脊椎动物发育过程中指定造血细胞命运至关重要.
- cdx4和hox基因协作建立后半皮体对血液发育的能力.
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