Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103, USA.
Dev Dyn. 2009 Nov;238(11):2745-59. doi: 10.1002/dvdy.22100.
Somites are segmental units of the mesoderm in vertebrate embryos that give rise to the axial skeleton, muscle, and dermis. Somitogenesis occurs in a periodic manner and is governed by a segmentation clock that causes cells to undergo repeated oscillations of gene expression. Here, we present a detailed analysis of cis-regulatory elements that control oscillating expression of the zebrafish her1 gene in the anterior presomitic mesoderm. We identify binding sites for Her proteins and demonstrate that they are necessary for transcriptional repression. This result confirms that direct negative autoregulation of her gene expression constitutes part of the oscillator mechanism. We also characterize binding sites for fused somites/Tbx24 and Suppressor of Hairless proteins and show that they are required for activation of her1 expression. These data provide the foundation for a precise description of the regulatory grammar that defines oscillating gene expression in the zebrafish segmentation clock.
体节是脊椎动物胚胎中中胚层的分段单位,它产生轴骨骼、肌肉和真皮。体节发生以周期性方式发生,并受分段时钟的控制,该时钟导致细胞反复进行基因表达的振荡。在这里,我们对控制斑马鱼前体节间充质中 her1 基因振荡表达的顺式调控元件进行了详细分析。我们确定了 Her 蛋白的结合位点,并证明它们对于转录抑制是必需的。这一结果证实了 her 基因表达的直接负反馈自我调节构成了振荡器机制的一部分。我们还对融合体节/Tbx24 和抑制毛形成蛋白的结合位点进行了表征,并表明它们对于 her1 表达的激活是必需的。这些数据为精确描述定义斑马鱼分节时钟中振荡基因表达的调控语法提供了基础。