Witze Eric S, Field Erin D, Hunt Donald F, Rothman Joel H
Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
Dev Biol. 2009 Mar 1;327(1):12-23. doi: 10.1016/j.ydbio.2008.11.015. Epub 2008 Dec 3.
The endoderm of C. elegans arises entirely from a single progenitor cell, the E blastomere, whose identity is specified by GATA type transcription factors, including END-1. In response to an inductive interaction mediated through Wnt/MAP kinase signaling pathways, POP-1, a Lef/Tcf-type transcription factor, restricts end-1 transcription to the posterior daughter of the mesendoderm progenitor (EMS cell), resulting in activation of endoderm differentiation by the SKN-1 and MED-1/2 transcription factors. We purified a factor from semi-synchronized early embryos that binds to an end-1 cis regulatory region critical for its endoderm-specific expression. Mass spectrometry identified this protein, PLP-1, as a C. elegans orthologue of the vertebrate pur alpha transcription factor. Expression of end-1 is attenuated in embryos depleted for PLP-1. While removal of plp-1 activity alone does not prevent endoderm development, it strongly enhances the loss of endoderm in mutants defective for the Wnt pathway. In contrast, loss of PLP-1 function does not synergize with mutants in the endoderm-inducing MAPK pathway. Moreover, nuclear localization of PLP-1 during interphase requires components of the MAPK pathway, suggesting that PLP-1 is influenced by MAPK signaling. PLP-1 is transiently asymmetrically distributed during cell divisions, with higher levels in the chromatin of the future posterior daughter of EMS and other dividing cells shortly after mitosis compared to that in their sisters. These findings imply that PLP-1 acts as a transcriptional activator of end-1 expression that may be modulated by MAPK signaling to promote endoderm development.
秀丽隐杆线虫的内胚层完全由单个祖细胞即E卵裂球产生,其身份由包括END-1在内的GATA型转录因子确定。响应通过Wnt/MAP激酶信号通路介导的诱导性相互作用,Lef/Tcf型转录因子POP-1将end-1转录限制在内中胚层祖细胞(EMS细胞)的后子代中,从而导致SKN-1和MED-1/2转录因子激活内胚层分化。我们从半同步化的早期胚胎中纯化了一种因子,该因子与对其在内胚层特异性表达至关重要的end-1顺式调控区域结合。质谱分析确定该蛋白PLP-1是脊椎动物pur alpha转录因子在秀丽隐杆线虫中的直系同源物。在缺乏PLP-1的胚胎中,end-1的表达减弱。虽然单独去除plp-1活性并不能阻止内胚层发育,但它会强烈增强Wnt通路缺陷突变体中内胚层的缺失。相反,PLP-1功能的丧失不会与内胚层诱导性MAPK通路中的突变体产生协同作用。此外,PLP-1在间期的核定位需要MAPK通路的组分,这表明PLP-1受MAPK信号传导的影响。PLP-1在细胞分裂期间短暂地不对称分布,与姐妹细胞相比,在有丝分裂后不久,EMS的未来后子代和其他分裂细胞的染色质中PLP-1水平更高。这些发现表明,PLP-1作为end-1表达的转录激活因子,可能受MAPK信号传导调节以促进内胚层发育。