Analysis of a Caenorhabditis elegans Twist homolog identifies conserved and divergent aspects of mesodermal patterning
Analysis of a Caenorhabditis elegans Twist homolog identifies conserved and divergent aspects of mesodermal patterning
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DOI：
10.1101/gad.12.16.2623
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发表时间：
1998-08-15
影响因子：
10.5
通讯作者：
Fire, A
中科院分区：
文献类型：
--
作者：
Harfe, BD;Gomes, AV;Fire, A
中胚层发育是一个多步骤的过程，其中细胞变得越来越特化以形成特定的组织类型。在果蝇和哺乳动物中，中胚层的适当分离和模式化涉及bHLH因子Twist。我们研究了一个扭曲相关的因素，CeTwist，秀丽隐杆线虫中胚层发育过程中的活动。C.秀丽线虫是由许多在早期谱系中被指定的独特的创始细胞衍生而来的！相反，单个胚细胞（M）负责胚后发育期间所有非性腺中胚层形成。使用免疫荧光和报告融合，我们确定的活性模式的基因编码CeTwist。在早期胚胎中胚层谱系的规范过程中没有观察到任何活性;相反，该基因在M谱系和一些具有非横纹肌命运的中胚层细胞中是活跃的。异位表达和遗传干扰试验表明CeTwist在胚后中胚层细胞命运规范中的作用。这些实验表明，CeTwist负责激活两个靶基因，这两个靶基因通常在来自M谱系的非横纹肌的特定亚群中表达。体外和体内实验表明，CeTwist与C. elegans E/Daughterless同源物直接激活这些靶标。我们研究的两个靶基因ceh-24和eg 1 -15分别编码NK-2类同源结构域和FGF受体（FGFR）同源物。Twist在果蝇中胚层模式形成期间激活FGFR和NK同源结构域靶基因，并且已提出类似的靶相互作用来调节脊椎动物头骨闭合期间的间充质生长。这些结果表明，一个保守的途径可能用于不同的功能，中胚层规格的可能性。
Mesodermal development is a multistep process in which cells become increasingly specialized to form specific tissue types. In Drosophila and mammals, proper segregation and patterning of the mesoderm involves the bHLH factor Twist. We investigated the activity of a Twist-related factor, CeTwist, during Caenorhabditis elegans mesoderm development. Embryonic mesoderm in C. elegans derives from a number of distinct founder cells that are specified during the early lineages! in contrast, a single blast cell (M) is responsible for all nongonadal mesoderm formation during postembryonic development. Using immunofluorescence and reporter fusions, we determined the activity pattern of the gene encoding CeTwist. No activity was observed during specification of mesodermal lineages in the early embryo; instead, the gene was active within the M lineage and in a number of mesodermal cells with nonstriated muscle fates. A role for CeTwist in postembryonic mesodermal cell fate specification was indicated by ectopic expression and genetic interference assays. These experiments showed that CeTwist was responsible for activating two target genes normally expressed in specific subsets of nonstriated muscles derived from the M lineage. In vitro and in vivo assays suggested that CeTwist cooperates with the C. elegans E/Daughterless homolog in directly activating these targets. The two target genes that we have studied, ceh-24 and eg1-15, encode an NK-2 class homeodomain and an FGF receptor (FGFR) homolog, respectively. Twist activates FGFR and NK-homeodomain target genes during mesodermal patterning of Drosophila and similar target interactions have been proposed to modulate mesenchymal growth during closure of the vertebrate skull. These results suggest the possibility that a conserved pathway may be used for diverse functions in mesodermal specification.