Caudal genes in blood development and leukemia
Caudal genes in blood development and leukemia
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DOI：
10.1111/j.1749-6632.2012.06625.x
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Daley, George Q.
中科院分区：
文献类型：
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作者：
Lengerke, Claudia;Daley, George Q.
尾基因家族的成员（在小鼠和人类中：Cdx 1，Cdx 2和Cdx 4）在早期发育过程中作为轴向伸长和前后图案的调节因子进行了研究。在成人中，Cdx 1和Cdx 2，而不是Cdx 4，已被深入探讨其在肠道组织稳态和胃肠道肿瘤的发病机制中的功能。胚胎造血的参与首先在斑马鱼中得到证实，其中cdx基因使后侧板中胚层能够对指定造血命运的基因做出反应，cdx基因中的复合突变因此导致无血表型。在斑马鱼胚胎和小鼠胚胎干细胞（ESC）中进行的平行研究描绘了鱼类和哺乳动物之间的保守途径，证实了血液发育过程中的BMP/Wnt-Cdx-Hox轴，可用于增强体外多能干细胞的血液祖细胞的衍生。Cdx基因的分子调控似乎很复杂，因为最近的数据表明参与了非Hox相关的机制，并存在由形态发生素控制的自动和交叉调控环。在这里，我们将审查Cdx基因在造血发育过程中的作用，通过比较斑马鱼和小鼠的影响，并讨论其参与恶性血液疾病。
Members of the caudal gene family (in mice and humans: Cdx1, Cdx2, and Cdx4) have been studied during early development as regulators of axial elongation and anteroposterior patterning. In the adult, Cdx1 and Cdx2, but not Cdx4, have been intensively explored for their function in intestinal tissue homeostasis and the pathogenesis of gastrointestinal cancers. Involvement in embryonic hematopoiesis was first demonstrated in zebrafish, where cdx genes render posterior lateral plate mesoderm competent to respond to genes specifying hematopoietic fate, and compound mutations in cdx genes thus result in a bloodless phenotype. Parallel studies performed in zebrafish embryos and murine embryonic stem cells (ESCs) delineate conserved pathways between fish and mammals, corroborating a BMP/Wnt-Cdx-Hox axis during blood development that can be employed to augment derivation of blood progenitors from pluripotent stem cells in vitro. The molecular regulation of Cdx genes appears complex, as more recent data suggest involvement of non-Hox-related mechanisms and the existence of auto-and cross-regulatory loops governed by morphogens. Here, we will review the role of Cdx genes during hematopoietic development by comparing effects in zebrafish and mice and discuss their participation in malignant blood diseases.