Baugh L Ryan, Hill Andrew A, Claggett Julia M, Hill-Harfe Kate, Wen Joanne C, Slonim Donna K, Brown Eugene L, Hunter Craig P
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Development. 2005 Apr;132(8):1843-54. doi: 10.1242/dev.01782. Epub 2005 Mar 16.
Maternal and zygotic activities of the homeodomain protein PAL-1 specify the identity and maintain the development of the multipotent C blastomere lineage in the C. elegans embryo. To identify PAL-1 regulatory target genes, we used microarrays to compare transcript abundance in wild-type embryos with mutant embryos lacking a C blastomere and to mutant embryos with extra C blastomeres. pal-1-dependent C-lineage expression was verified for select candidate target genes by reporter gene analysis, though many of the target genes are expressed in additional lineages as well. The set of validated target genes includes 12 transcription factors, an uncharacterized wingless ligand and five uncharacterized genes. Phenotypic analysis demonstrates that the identified PAL-1 target genes affect specification, differentiation and morphogenesis of C-lineage cells. In particular, we show that cell fate-specific genes (or tissue identity genes) and a posterior HOX gene are activated in lineage-specific fashion. Transcription of targets is initiated in four temporal phases, which together with their spatial expression patterns leads to a model of the regulatory network specified by PAL-1.
同源域蛋白PAL-1的母体活性和合子活性决定了秀丽隐杆线虫胚胎中多能C卵裂球谱系的特性,并维持其发育。为了鉴定PAL-1的调控靶基因,我们使用微阵列比较野生型胚胎与缺乏C卵裂球的突变胚胎以及具有额外C卵裂球的突变胚胎中的转录本丰度。通过报告基因分析验证了部分候选靶基因的pal-1依赖性C谱系表达,不过许多靶基因也在其他谱系中表达。已验证的靶基因集包括12种转录因子、一种未鉴定的无翅型配体和5个未鉴定的基因。表型分析表明,所鉴定的PAL-1靶基因影响C谱系细胞的特化、分化和形态发生。特别是,我们发现细胞命运特异性基因(或组织特性基因)和一个后部HOX基因以谱系特异性方式被激活。靶标的转录在四个时间阶段启动,这与它们的空间表达模式共同形成了由PAL-1指定的调控网络模型。