Retinoid signalling is required for information transfer from mesoderm to neuroectoderm during gastrulation
Retinoid signalling is required for information transfer from mesoderm to neuroectoderm during gastrulation
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DOI：
10.1387/ijdb.082705fl
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发表时间：
2010-01-01
影响因子：
0.7
通讯作者：
Durston, Antony J.
中科院分区：
文献类型：
--
作者：
Lloret-Vilaspasa, Ferran;Jansen, Hans J.;Durston, Antony J.
脊椎动物中枢神经系统（CNS）的后脑区域呈现复杂的区域化。它由7-8个不同的形态学片段组成，称为菱形节，每个片段具有由转录因子组合提供的独特身份。一类信号分子，类维生素A，已被证明是至关重要的后脑图案通过直接反式激活的神经外胚层中的Hoxgenes。然而，这种形态发生素的作用方式尚未完全了解。在这里，我们表明，类维生素A受体拮抗剂AGN 193109导致非洲爪蟾后后脑缺陷，在其他脊椎动物中看到的。我们发现，这种缺陷出现在原肠胚形成。在原肠胚形成过程中阻断内源性类维生素A活性导致原肠胚神经外胚层中大多数3个Hox基因（旁系同源物1-5）下调，但它们在原肠胚非组织者中胚层中的初始激活不受影响。在禽类胚胎中也得到了类似的结果：维生素A缺乏的鹌鹑胚胎中，3'端Hox基因（即Hoxb 1，Hoxb 4）在神经管中的表达缺陷，但它们在原条和新兴的近轴和侧中胚层中的早期表达不受影响。在非洲爪蟾中，通过靶向注射视黄酸分解代谢酶xCYP 26和细胞视黄酸结合蛋白xCRABP的mRNA从中胚层消耗类视黄酸，阻断了上覆神经外胚层中的3' Hox基因表达。我们建议，原肠胚非组织者中胚层及其后来的衍生物，近轴中胚层，是类维生素A的来源，它作为一个“转化”（caudalising）的信号，为未来的后后脑。
The hindbrain region of the vertebrate central nervous system (CNS) presents a complex regionalisation. It consists of 7-8 distinct morphological segments called rhombomeres, each with a unique identity provided by combinations of transcription factors. One class of signalling molecules, retinoids, have been shown to be crucial for hindbrain patterning through direct trans-activation of Hoxgenes in the neuroectoderm. However, how this morphogen acts is not yet fully understood. Here, we show that the retinoid receptor antagonist AGN193109 causes a posterior hindbrain defect in Xenopus, comparable to that seen in other vertebrates. We show that this defect arises during gastrulation. Blocking endogenous retinoid activity during gastrulation causes downregulation of the most 3 Hox genes (paralogues 1-5) in gastrula neuroectoderm, but their initial activation in gastrula non-organiser mesoderm is unaffected. Similar results were obtained in avian embryos: Vitamin A-deficient quail embryos have defective expression of 3' Hox genes (i.e. Hoxb1, Hoxb4) in the neural tube, but their early expression in the primitive streak and emerging paraxial and lateral mesoderm is not affected. In Xenopus, depletion of retinoids from mesoderm by targeted injection of mRNAs for the retinoic acid catabolising enzyme xCYP26 and the cellular retinoic acid binding protein xCRABP blocks 3' Hox gene expression in the overlying neuroectoderm. We propose that the gastrula non-organiser mesoderm and its later derivative, the paraxial mesoderm, is the source of a retinoid, which acts as a "transforming" (caudalising) signal for the future posterior hindbrain.