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在发育中的斑马鱼内胚层中,多个核糖体蛋白表达水平较高,并且对于正常的外分泌胰腺发育是必需的。

Multiple ribosomal proteins are expressed at high levels in developing zebrafish endoderm and are required for normal exocrine pancreas development.

机构信息

Department of Surgery, Johns Hopkins University , Baltimore, MD 21205, USA.

出版信息

Zebrafish. 2013 Jun;10(2):161-9. doi: 10.1089/zeb.2013.0884. Epub 2013 May 22.

Abstract

Ribosomal protein L (rpl) genes are essential for assembly of the 60S subunit of the eukaryotic ribosome and may also carry out additional extra-ribosomal functions. We have identified a common expression pattern for rpl genes in developing zebrafish larvae. After initially widespread expression in early embryos, the expression of multiple rpl genes becomes increasingly restricted to the endoderm. With respect to the pancreas, rpl genes are highly expressed in ptf1a-expressing pancreatic progenitors at 48 hpf, suggesting possible functional roles in pancreatic morphogenesis and/or differentiation. Utilizing two available mutant lines, rpl23a(hi2582) and rpl6(hi3655b), we found that ptf1a-expressing pancreatic progenitors fail to properly expand in embryos homozygous for either of these genes. In addition to these durable homozygous phenotypes, we also demonstrated recoverable delays in ptf1a-expressing pancreatic progenitor expansion in rpl23a(hi2582) and rpl6(hi3655b) heterozygotes. Disruptions in ribosome assembly are generally understood to initiate a p53-dependent cellular stress response. However, concomitant p53 knockdown was unable to rescue normal pancreatic progenitor expansion in either rpl23a(hi2582) or rpl6(hi3655b) mutant embryos, suggesting required and p53-independent roles for rpl23a and rpl6 in pancreas development.

摘要

核糖体蛋白 L(rpl)基因对于真核核糖体 60S 亚基的组装是必不可少的,并且可能还具有额外的核糖体外功能。我们已经确定了发育中的斑马鱼幼虫中 rpl 基因的共同表达模式。在早期胚胎中最初广泛表达后,多个 rpl 基因的表达逐渐局限于内胚层。就胰腺而言,rpl 基因在 48 hpf 时在表达 ptf1a 的胰腺祖细胞中高度表达,这表明它们在胰腺形态发生和/或分化中可能具有功能作用。利用两个可用的突变体系 rpl23a(hi2582)和 rpl6(hi3655b),我们发现这些基因纯合的胚胎中,表达 ptf1a 的胰腺祖细胞不能正常扩增。除了这些持久的纯合表型外,我们还在 rpl23a(hi2582)和 rpl6(hi3655b)杂合子中证明了 ptf1a 表达的胰腺祖细胞扩增存在可恢复的延迟。核糖体组装的破坏通常被理解会引发依赖 p53 的细胞应激反应。然而,同时敲低 p53 并不能挽救 rpl23a(hi2582)或 rpl6(hi3655b)突变体胚胎中正常的胰腺祖细胞扩增,这表明 rpl23a 和 rpl6 在胰腺发育中具有必需的和不依赖 p53 的作用。

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