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分析 her1 和 her7 突变体揭示了体节时钟模块的时空分离。

Analysis of her1 and her7 mutants reveals a spatio temporal separation of the somite clock module.

机构信息

Institute for Genetics, University to Cologne, Koeln, Germany.

出版信息

PLoS One. 2012;7(6):e39073. doi: 10.1371/journal.pone.0039073. Epub 2012 Jun 18.

Abstract

Somitogenesis is controlled by a genetic network consisting of an oscillator (clock) and a gradient (wavefront). The "hairy and Enhancer of Split"- related (her) genes act downstream of the Delta/Notch (D/N) signaling pathway, and are crucial components of the segmentation clock. Due to genome duplication events, the zebrafish genome, possesses two gene copies of the mouse Hes7 homologue: her1 and her7. To better understand the functional consequences of this gene duplication, and to determine possible independent roles for these two genes during segmentation, two zebrafish mutants her1(hu2124) and her7(hu2526) were analyzed. In the course of embryonic development, her1(hu2124) mutants exhibit disruption of the three anterior-most somite borders, whereas her7(hu2526) mutants display somite border defects restricted to somites 8 (+/-3) to 17 (+/-3) along the anterior-posterior axis. Analysis of the molecular defects in her1(hu2124) mutants reveals a her1 auto regulatory feedback loop during early somitogenesis that is crucial for correct patterning and independent of her7 oscillation. This feedback loop appears to be restricted to early segmentation, as cyclic her1 expression is restored in her1(hu2124) embryos at later stages of development. Moreover, only the anterior deltaC expression pattern is disrupted in the presomitic mesoderm of her1(hu2124) mutants, while the posterior expression pattern of deltaC remains unaltered. Together, this data indicates the existence of an independent and genetically separable anterior and posterior deltaC clock modules in the presomitic mesdorm (PSM).

摘要

体节发生由一个由振荡器(时钟)和梯度(波前)组成的遗传网络控制。“毛发和 Splitter 增强子”(her)基因位于 Delta/Notch(D/N)信号通路的下游,是分段时钟的关键组成部分。由于基因组复制事件,斑马鱼基因组拥有两个 mouse Hes7 同源物基因的拷贝:her1 和 her7。为了更好地理解这种基因复制的功能后果,并确定这两个基因在分段过程中可能具有独立的作用,分析了两个斑马鱼突变体 her1(hu2124)和 her7(hu2526)。在胚胎发育过程中,her1(hu2124)突变体表现出三个最前体节边界的破坏,而 her7(hu2526)突变体则显示出体节边界缺陷,仅限于沿前后轴的体节 8(+/-3)到 17(+/-3)。对 her1(hu2124)突变体的分子缺陷分析表明,在早期体节发生过程中存在一个 her1 自动调节反馈回路,这对于正确的模式形成是至关重要的,并且独立于 her7 振荡。这个反馈回路似乎仅限于早期的分段,因为在发育的后期阶段,her1(hu2124)胚胎中循环的 her1 表达得到恢复。此外,只有在 her1(hu2124)突变体的前体节中,前 deltaC 的表达模式被破坏,而后 deltaC 的表达模式保持不变。总之,这些数据表明,在前体节间充质(PSM)中存在一个独立的、遗传上可分离的前和后 deltaC 时钟模块。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ac5/3377618/0f3737b2f8d1/pone.0039073.g001.jpg

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