Liu J, Fire A
Carnegie Institution of Washington, Department of Embryology, Baltimore, MD 21210, USA.
Development. 2000 Dec;127(23):5179-90. doi: 10.1242/dev.127.23.5179.
Members of the Hox family of homeoproteins and their cofactors play a central role in pattern formation of all germ layers. During postembryonic development of C. elegans, non-gonadal mesoderm arises from a single mesoblast cell M. Starting in the first larval stage, M divides to produce 14 striated muscles, 16 non-striated muscles, and two non-muscle cells (coelomocytes). We investigated the role of the C. elegans Hox cluster and of the exd ortholog ceh-20 in patterning of the postembryonic mesoderm. By examining the M lineage and its differentiation products in different Hox mutant combinations, we found an essential but overlapping role for two of the Hox cluster genes, lin-39 and mab-5, in diversification of the postembryonic mesoderm. This role of the two Hox gene products required the CEH-20 cofactor. One target of these two Hox genes is the C. elegans twist ortholog hlh-8. Using both in vitro and in vivo assays, we demonstrated that twist is a direct target of Hox activation. We present evidence from mutant phenotypes that twist is not the only target for Hox genes in the M lineage: in particular we show that lin-39 mab-5 double mutants exhibit a more severe M lineage defect than the hlh-8 null mutant.
同源异型结构域蛋白的Hox家族成员及其辅助因子在所有胚层的模式形成中起着核心作用。在秀丽隐杆线虫的胚后发育过程中，非性腺中胚层起源于单个中胚层细胞M。从第一幼虫阶段开始，M细胞分裂产生14条横纹肌、16条平滑肌和两个非肌肉细胞（体腔细胞）。我们研究了秀丽隐杆线虫Hox基因簇以及exd直系同源基因ceh-20在胚后中胚层模式形成中的作用。通过检查不同Hox突变组合中的M细胞谱系及其分化产物，我们发现Hox基因簇中的两个基因lin-39和mab-5在胚后中胚层多样化中起着重要但重叠的作用。这两个Hox基因产物的这一作用需要CEH-20辅助因子。这两个Hox基因的一个靶标是秀丽隐杆线虫twist直系同源基因hlh-8。通过体外和体内试验，我们证明twist是Hox激活的直接靶标。我们从突变体表型中提供证据表明，twist不是M细胞谱系中Hox基因的唯一靶标：特别是我们表明，lin-39 mab-5双突变体表现出比hlh-8基因敲除突变体更严重的M细胞谱系缺陷。
