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首页> 外文期刊>Development >Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development.
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Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development.

机译:Cyp26酶产生后脑发育所必需的视黄酸反应模式。

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摘要

Retinoic acid (RA) is essential for normal vertebrate development, including the patterning of the central nervous system. During early embryogenesis, RA is produced in the trunk mesoderm through the metabolism of vitamin A derived from the maternal diet and behaves as a morphogen in the developing hindbrain where it specifies nested domains of Hox gene expression. The loss of endogenous sources of RA can be rescued by treatment with a uniform concentration of exogenous RA, indicating that domains of RA responsiveness can be shaped by mechanisms other than the simple diffusion of RA from a localized posterior source. Here, we show that the cytochrome p450 enzymes of the Cyp26 class, which metabolize RA into polar derivatives, function redundantly to shape RA-dependent gene-expression domains during hindbrain development. In zebrafish embryos depleted of the orthologs of the three mammalian CYP26 genes CYP26A1, CYP26B1 and CYP26C1, the entire hindbrain expresses RA-responsive genes that are normally restricted to nested domains in the posterior hindbrain. Furthermore, we show that Cyp26 enzymes are essential for exogenous RA to rescue hindbrain patterning in RA-depleted embryos. We present a ;gradient-free' model for hindbrain patterning in which differential RA responsiveness along the hindbrain anterior-posterior axis is shaped primarily by the dynamic expression of RA-degrading enzymes.
机译:维甲酸(RA)对于正常的脊椎动物发育(包括中枢神经系统的模式)至关重要。在早期胚胎发生过程中,RA通过母体饮食中的维生素A代谢在躯干中胚层中产生,并在发育中的后脑中充当形态发生子,在那里它指定了Hox基因表达的嵌套域。 RA的内源性来源的丢失可以通过用均一浓度的外源性RA进行治疗来挽救,这表明RA响应域可能是由R​​A从局部后源简单扩散以外的机制所决定的。在这里,我们显示Cyp26类的细胞色素p450酶将RA代谢成极性衍生物,并在后脑发育过程中冗余发挥作用来塑造RA依赖性基因表达域。在斑马鱼胚胎中,缺失了三个哺乳动物CYP26基因CYP26A1,CYP26B1和CYP26C1的直系同源基因后,整个后脑表达的RA反应基因通常局限于后部后脑的嵌套结构域。此外,我们表明Cyp26酶对于外源RA抢救RA耗尽的胚胎中的后脑模式至关重要。我们为后脑模式提出了一种“无梯度”模型,其中沿后脑前后轴的不同RA反应性主要是由RA降解酶的动态表达形成的。

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