Relaix F, Weng X, Marazzi G, Yang E, Copeland N, Jenkins N, Spence S E, Sassoon D
Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Dev Biol. 1996 Aug 1;177(2):383-96. doi: 10.1006/dbio.1996.0172.
The cellular and molecular processes leading to the establishment of the skeletal muscle lineage in the vertebrate are not well understood. The MyoD-related family of myogenic regulatory factors (MRFs) are expressed during somitogenesis although cells with myogenic capacity are present prior to gastrulation. We propose that regulatory genes exist that guide the skeletal muscle lineage during early development. In an effort to identify these regulatory genes, we performed a differential screening to isolate transcripts that are present in myogenic cells and in the embryo prior to MRF expression but absent in nonmyogenic fibroblasts. We report here the identification of Pw1. The Pw1 transcript is approximately 8.5 kb long and encodes a large protein containing 12 widespread C2H2 zinc fingers and 3 motifs containing periodic prolines and acidic residues. Consistent with the possibility that Pw1 is a transcription factor, we observe nuclear localization of the protein. Pw1 is strongly expressed upon gastrulation and subsequently becomes restricted to skeletal muscle and subregions of the central nervous system. Pw1 is initially expressed in all mesodermal cells early in development; however, its maintained expression in adult differentiated muscle suggests a specific role in the skeletal muscle lineage. Pw1 expression is cell cycle specific with levels highest during late M-phase. The gene is intronless which may facilitate transcription during cell division. At present, the precise function of Pw1 is not understood; however, we note that Pw1 maps to the proximal region of chromosome 7 near the axial segmentation mutant pudgy which shows severe perturbation of axial skeletal and muscle structures.
脊椎动物中导致骨骼肌谱系建立的细胞和分子过程尚未完全明了。尽管在原肠胚形成之前就已存在具有成肌能力的细胞,但成肌调节因子(MRF)的MyoD相关家族在体节发生过程中表达。我们提出,在早期发育过程中存在引导骨骼肌谱系的调节基因。为了鉴定这些调节基因,我们进行了差异筛选,以分离在成肌细胞和胚胎中、在MRF表达之前存在但在非成肌成纤维细胞中不存在的转录本。我们在此报告Pw1的鉴定。Pw1转录本约8.5 kb长,编码一种大型蛋白质,该蛋白质含有12个广泛分布的C2H2锌指以及3个含有周期性脯氨酸和酸性残基的基序。与Pw1可能是一种转录因子的可能性一致,我们观察到该蛋白质的核定位。Pw1在原肠胚形成时强烈表达,随后局限于骨骼肌和中枢神经系统的亚区域。Pw1最初在发育早期的所有中胚层细胞中表达;然而,其在成年分化肌肉中的持续表达表明它在骨骼肌谱系中具有特定作用。Pw1的表达具有细胞周期特异性,在M期后期水平最高。该基因无内含子,这可能有助于在细胞分裂期间进行转录。目前,Pw还不清楚;然而,我们注意到Pw1定位于7号染色体的近端区域,靠近轴向分割突变体矮胖基因,该突变体显示出轴向骨骼和肌肉结构的严重紊乱。