sox4b is a key player of pancreatic α cell differentiation in zebrafish
sox4b is a key player of pancreatic α cell differentiation in zebrafish
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DOI：
10.1016/j.ydbio.2005.06.024
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发表时间：
2005-09-01
影响因子：
2.7
通讯作者：
Peers, B
中科院分区：
文献类型：
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作者：
Mavropoulos, A;Devos, N;Peers, B
胰腺的发育依赖于主要属于同源域和基本Helix-Loop-Helix家族的转录因子网络。我们在这项研究中表明，在斑马鱼中，sox4是sry样HMG-box （SOX）家族的一员，是正常内分泌细胞分化所必需的。我们发现斑马鱼中存在两个与哺乳动物Sox4同源的基因，其中只有一个sox4b在胰腺组织中强烈表达。sox4b转录本在5-somite阶段的中干内胚层中被检测到，远早于早期胰腺基因pdx-1的表达开始。此外，通过荧光双原位杂交，我们发现sox4b的表达主要局限于内分泌室的前体。这种表达在分化细胞中不能维持，但在a细胞和一些β细胞中可以检测到瞬时表达。表达sox4b的细胞属于内分泌谱系，这进一步证明了它们在慢肌缺失突变胚胎的胰腺中缺失，这些胚胎缺乏所有早期内分泌标志物，但保留了外分泌标志物的表达。sox4b参与细胞分化，首先是通过其在心智炸弹突变胚胎中表达上调，表现出胰腺细胞加速分化。此外，sox4b基因敲除导致胰高血糖素表达急剧下降，而其他胰腺标志物包括胰岛素、生长抑素和胰蛋白酶则不受显著影响。这种细胞分化的中断是由于在胰腺中特异性下调同源盒arx基因。综上所述，这些数据表明，在斑马鱼中，sox4b在内分泌细胞分化过程中短暂表达，在α内分泌细胞的产生中起着至关重要的作用。(c) 2005爱思唯尔公司版权所有。
Pancreas development relies on a network of transcription factors belonging mainly to the Homeodomain and basic Helix-Loop-Helix families. We show in this study that, in zebrafish, sox4, a member of the SRY-like HMG-box (SOX) family, is required for proper endocrine cell differentiation. We found that two genes orthologous to mammalian Sox4 are present in zebrafish and that only one of them, sox4b, is strongly expressed in the pancreatic anlage. Transcripts of sox4b were detected in mid-trunk endoderm from the 5-somite stage, well before the onset of expression of the early pancreatic gene pdx-1. Furthermore, by fluorescent double in situ hybridization, we found that expression of sox4b is mostly restricted to precursors of the endocrine compartment. This expression is not maintained in differentiated cells although transient expression can be detected in a cells and some beta cells. That sox4b-expressing cells belong to the endocrine lineage is further illustrated by their absence from the pancreata of slow-muscle-omitted mutant embryos, which specifically lack all early endocrine markers while retaining expression of exocrine markers. The involvement of sox4b in cell differentiation is suggested firstly by its up-regulation in mind bomb mutant embryos displaying accelerated pancreatic cell differentiation. In addition, sox4b knock-down leads to a drastic reduction in glucagon expression, while other pancreatic markers including insulin, somatostatin, and trypsin are not significantly affected. This disruption of a cell differentiation is due to down-regulation of the homeobox arx gene specifically in the pancreas. Taken together, these data demonstrate that, in zebrafish, sox4b is expressed transiently during endocrine cell differentiation and plays a crucial role in the generation of alpha endocrine cells. (c) 2005 Elsevier Inc. All rights reserved.