Kobberup Sune, Nyeng Pia, Juhl Kirstine, Hutton John, Jensen Jan
Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, Colorado 80045, USA.
Dev Dyn. 2007 Nov;236(11):3100-10. doi: 10.1002/dvdy.21292.
ETS-family factors play major roles in development and cancer, notably as critical targets for extra-cellular signaling pathways, including MAPK-signaling. Given the presently limited knowledge on the role of ETS-factors in pancreatic development, we here sought to characterize all 26 individual members of the ETS-family in relation to pancreatic development using a combination of genomics, RT-PCR, and histological techniques. This analysis uncovers 22 ETS family genes displaying select spatial and temporal expression patterns in the developing pancreas. Highly specific expression of ETS-family components is observed in pancreatic progenitor cells or the associated embryonic mesenchyme. Other members are linked to the differentiation of more mature pancreatic cells, including exocrine and endocrine cell types. We find that two members of the Etv subfamily, Etv4 and Etv5, are expressed in cells proximal to pancreatic mesenchyme, and, furthermore, induced in FGF10-arrested pancreatic progenitors suggesting that these factors mediate mesenchymal-to-epithelial signaling.
ETS 家族因子在发育和癌症中发挥着重要作用,尤其是作为细胞外信号通路(包括 MAPK 信号通路)的关键靶点。鉴于目前关于 ETS 因子在胰腺发育中作用的知识有限,我们在此试图通过基因组学、逆转录聚合酶链反应(RT-PCR)和组织学技术相结合的方法,来描述 ETS 家族的所有 26 个成员与胰腺发育的关系。该分析揭示了 22 个 ETS 家族基因在发育中的胰腺中呈现出特定的时空表达模式。在胰腺祖细胞或相关的胚胎间充质中观察到 ETS 家族成分的高度特异性表达。其他成员则与更成熟的胰腺细胞(包括外分泌和内分泌细胞类型)的分化有关。我们发现 Etv 亚家族的两个成员 Etv4 和 Etv5 在胰腺间充质附近的细胞中表达,此外,在 FGF10 阻滞的胰腺祖细胞中被诱导表达,这表明这些因子介导间充质到上皮的信号传导。