Dynamics of Sonic hedgehog signaling in the ventral spinal cord are controlled by intrinsic changes in source cells requiring Sulfatase 1
Dynamics of Sonic hedgehog signaling in the ventral spinal cord are controlled by intrinsic changes in source cells requiring Sulfatase 1
复制标题
DOI：
10.1242/dev.101717
复制
发表时间：
2014-03-15
期刊：
影响因子：
4.6
通讯作者：
Soula, Cathy
中科院分区：
文献类型：
--
作者：
Al Oustah, Amir;Danesin, Cathy;Soula, Cathy
在腹侧脊髓中，神经元和神经胶质细胞亚型的生成由音刺猬 (Shh) 控制。这种形态发生素通过调节发育过程中基因表达的空间和时间序列来促进细胞多样性。在这里，我们报告说，建立Shh源细胞不足以诱导斑马鱼在正确的时间和地点顺序生成腹侧中间神经元和少突胶质细胞所需的高阈值反应。相反，我们发现，产生 Shh 的细胞必须在发育的两个关键时间点反复上调分泌的硫酸酯酶 1 (Sulf1)，才能达到其完全诱导能力。我们提供的证据表明，Sulf1 触发 Shh 信号传导活动，以建立并随后修改腹侧神经祖细胞中基因表达的空间排列。我们进一步提出了支持Sulf1通过刺激Shh活性形式的产生来控制Shh时间活动的论据。我们的工作通过指出Sulf1在调节Shh依赖性神经细胞多样性中的关键作用，强调了一种新的调节水平，其中涉及Shh源特性的时间演化。
In the ventral spinal cord, generation of neuronal and glial cell subtypes is controlled by Sonic hedgehog (Shh). This morphogen contributes to cell diversity by regulating spatial and temporal sequences of gene expression during development. Here, we report that establishing Shh source cells is not sufficient to induce the high-threshold response required to specify sequential generation of ventral interneurons and oligodendroglial cells at the right time and place in zebrafish. Instead, we show that Shh-producing cells must repeatedly upregulate the secreted enzyme Sulfatase 1 (Sulf1) at two critical time points of development to reach their full inductive capacity. We provide evidence that Sulf1 triggers Shh signaling activity to establish and, later on, modify the spatial arrangement of gene expression in ventral neural progenitors. We further present arguments in favor of Sulf1 controlling Shh temporal activity by stimulating production of active forms of Shh from its source. Our work, by pointing out the key role of Sulf1 in regulating Shh-dependent neural cell diversity, highlights a novel level of regulation, which involves temporal evolution of Shh source properties.