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首页> 外文期刊>Development >Independent regulation of initiation and maintenance phases of Hoxa3 expression in the vertebrate hindbrain involve auto- and cross-regulatory mechanisms.
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Independent regulation of initiation and maintenance phases of Hoxa3 expression in the vertebrate hindbrain involve auto- and cross-regulatory mechanisms.

机译：脊椎动物后脑中Hoxa3表达的启动和维持阶段的独立调节涉及自动调节和交叉调节机制。

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During development of the vertebrate hindbrain, Hox genes play multiple roles in the segmental processes that regulate anteroposterior (AP) patterning. Paralogous Hox genes, such as Hoxa3, Hoxb3 and Hoxd3, generally have very similar patterns of expression, and gene targeting experiments have shown that members of paralogy group 3 can functionally compensate for each other. Hence, distinct functions for individual members of this family may primarily depend upon differences in their expression domains. The earliest domains of expression of the Hoxa3 and Hoxb3 genes in hindbrain rhombomeric (r) segments are transiently regulated by kreisler, a conserved Maf b-Zip protein, but the mechanisms that maintain expression in later stages are unknown. In this study, we have compared the segmental expression and regulation of Hoxa3 and Hoxb3 in mouse and chick embryos to investigate how they are controlled after initial activation. We found that the patterns of Hoxa3 and Hoxb3 expression in r5 and r6 in later stages during mouse and chick hindbrain development were differentially regulated. Hoxa3 expression was maintained in r5 and r6, while Hoxb3 was downregulated. Regulatory comparisons of cis-elements from the chick and mouse Hoxa3 locus in both transgenic mouse and chick embryos have identified a conserved enhancer that mediates the late phase of Hoxa3 expression through a conserved auto/cross-regulatory loop. This block of similarity is also present in the human and horn shark loci, and contains two bipartite Hox/Pbx-binding sites that are necessary for its in vivo activity in the hindbrain. These HOX/PBC sites are positioned near a conserved kreisler-binding site (KrA) that is involved in activating early expression in r5 and r6, but their activity is independent of kreisler. This work demonstrates that separate elements are involved in initiating and maintaining Hoxa3 expression during hindbrain segmentation, and that it is regulated in a manner different from Hoxb3 in later stages. Together, these findings add further strength to the emerging importance of positive auto- and cross-regulatory interactions between Hox genes as a general mechanism for maintaining their correct spatial patterns in the vertebrate nervous system.
机译：在脊椎动物后脑的发育过程中，Hox基因在调节前后（AP）模式的节段过程中发挥多种作用。同源的Hox基因（例如Hoxa3，Hoxb3和Hoxd3）通常具有非常相似的表达模式，并且基因靶向实验已显示，paralogy组3的成员可以在功能上相互补偿。因此，该家族个体成员的不同功能可能主要取决于其表达域的差异。后脑菱形（r）段中Hoxa3和Hoxb3基因的最早表达域是由kreisler（一种保守的Maf b-Zip蛋白）瞬时调控的，但在后期维持表达的机制尚不清楚。在这项研究中，我们比较了Hoxa3和Hoxb3在小鼠和雏鸡胚胎中的节段表达和调控，以研究它们在初始激活后如何受到控制。我们发现在小鼠和鸡后脑发育的后期r5和r6中Hoxa3和Hoxb3表达的模式受到差异调节。 Hoxa3表达在r5和r6中得以维持，而Hoxb3被下调。在转基因小鼠和雏鸡胚胎中，来自雏鸡和小鼠Hoxa3基因座的顺式元件的调控比较已鉴定出保守的增强子，其通过保守的自动/交叉调控环介导Hoxa3表达的晚期。人类和角鲨基因座中也存在这种相似性，并且包含两个二分体Hox / Pbx结合位点，这是其在后脑中的体内活性所必需的。这些HOX / PBC位点位于保守的kreisler结合位点（KrA）附近，该位点与激活r5和r6中的早期表达有关，但它们的活性与kreisler无关。这项工作表明在后脑分割过程中启动和维持Hoxa3表达涉及单独的元素，并在后期阶段以不同于Hoxb3的方式进行调节。总之，这些发现进一步增强了Hox基因之间正向自调控和交叉调控相互作用的重要性，这是在脊椎动物神经系统中维持其正确空间格局的一般机制。

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