Zebrafish Gli3 functions as both an activator and a repressor in Hedgehog signaling.
Zebrafish Gli3 functions as both an activator and a repressor in Hedgehog signaling.
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DOI：
10.1016/j.ydbio.2004.10.003
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发表时间：
2005-01
影响因子：
2.7
通讯作者：
O. Tyurina;B. Guner;E. Popova;Jianchi Feng;A. Schier;J. Kohtz;R. Karlstrom
中科院分区：
文献类型：
--
作者：
O. Tyurina;B. Guner;E. Popova;Jianchi Feng;A. Schier;J. Kohtz;R. Karlstrom
Hedgehog(HH)信号调节多种胚胎组织中的细胞分化和模式。在脊椎动物中，至少有三种Gli转录因子(Gli1、Gli2和Gli3)参与HH信号转导。比较研究表明斑马鱼和小鼠对Gli1和Gli2的需求不同。在这里，我们解决了斑马鱼Gli3功能是否也发生了分化的问题，并分析了HH信号和Gli活性之间的调控相互作用。我们发现斑马鱼Gli3具有早期激活HH靶基因的功能，该基因与腹侧神经管中的Gli1激活功能重叠。体外报告分析表明，在高浓度HH存在的情况下，Gli3与Gli1协同激活转录。在体细胞发育的后期，Gli3被需要作为HH反应的抑制因子。Gli3和Gli2在背侧脊髓、后脑和中脑都有这种抑制活性，但在前脑没有。斑马鱼Gli3一直在体外阻断Gli1介导的报告基因的激活。在眼睛中，Gli3也是正常表达ath5和视网膜神经节细胞(RGC)分化所必需的。这些结果揭示了Gli3在脊椎动物发育中的保守作用，并揭示了新的区域功能和GliI基因之间的调控相互作用。
Hedgehog (Hh) signaling regulates cell differentiation and patterning in a wide variety of embryonic tissues. In vertebrates, at least three Gli transcription factors (Gli1, Gli2, and Gli3) are involved in Hh signal transduction. Comparative studies have revealed divergent requirements for Gli1 and Gli2 in zebrafish and mouse. Here, we address the question of whether Gli3 function has also diverged in zebrafish and analyze the regulatory interactions between Hh signaling and Gli activity. We find that zebrafish Gli3 has an early function as an activator of Hh target genes that overlaps with Gli1 activator function in the ventral neural tube. In vitro reporter analysis shows that Gli3 cooperates with Gli1 to activate transcription in the presence of high concentrations of Hh. During late somitogenesis stages, Gli3 is required as a repressor of the Hh response. Gli3 shares this repressor activity with Gli2 in the dorsal spinal cord, hindbrain, and midbrain, but not in the forebrain. Consistently, zebrafish Gli3 blocks Gli1-mediated activation of a reporter gene in the absence of Hh in vitro. In the eye, Gli3 is also required for proper ath5 expression and the differentiation of retinal ganglion cells (RGCs). These results reveal a conserved role for Gli3 in vertebrate development and uncover novel regional functions and regulatory interactions among gli genes.