The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite
The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite
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DOI：
10.1242/dev.000836
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发表时间：
2007-04-15
期刊：
影响因子：
4.6
通讯作者：
Saga, Yumiko
中科院分区：
文献类型：
--
作者：
Morimoto, Mitsuru;Sasaki, Nobuo;Saga, Yumiko
Mesp2转录因子在节段边界的形成和在体内的直立-尾端模式的建立中起着重要的作用。一个可能的Mesp2靶基因Ripply2在Mesp2缺失的小鼠中被微阵列鉴定为下调。Ripply2编码一个含有WRPW基序的推定转录共抑制子。我们发现Mesp2与Ripply2基因增强子结合，表明Ripply2是Mesp2的直接靶点。然后，我们通过产生Ripply2敲除小鼠来检查Ripply2是否负责抑制Mesp2控制下的基因。出乎意料的是，ripply2基因缺失的胚胎与mesp2基因缺失的小鼠相比，表现出了一种巢化表型。基因表达研究和遗传分析进一步揭示了Ripply2是Mesp2的负调控因子，Ripply2基因的缺失导致Mesp2的表达延长，通过抑制Notch信号导致表型的逆转。我们的研究表明，Ripply2-Mesp2负反馈回路对于在一个体体内周期性地产生直立-尾侧极性是必不可少的。
The Mesp2 transcription factor plays essential roles in segmental border formation and in the establishment of rostro-caudal patterning within a somite. A possible Mesp2 target gene, Ripply2, was identified by microarray as being downregulated in the Mesp2-null mouse. Ripply2 encodes a putative transcriptional co-repressor containing a WRPW motif. We find that Mesp2 binds to the Ripply2 gene enhancer, indicating that Ripply2 is a direct target of Mesp2. We then examined whether Ripply2 is responsible for the repression of genes under the control of Mesp2 by generating a Ripply2-knockout mouse. Unexpectedly, Ripply2-null embryos show a rostralized phenotype, in contrast to Mesp2-null mice. Gene expression studies together with genetic analyses further revealed that Ripply2 is a negative regulator of Mesp2 and that the loss of the Ripply2 gene results in the prolonged expression of Mesp2, leading to a rostralized phenotype via the suppression of Notch signaling. Our study demonstrates that a Ripply2-Mesp2 negative-feedback loop is essential for the periodic generation of the rostro-caudal polarity within a somite.