Cellular differentiation in the emerging fetal rat small intestinal epithelium: mosaic patterns of gene expression.
Cellular differentiation in the emerging fetal rat small intestinal epithelium: mosaic patterns of gene expression.
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新生胎鼠小肠上皮的细胞分化：基因表达的马赛克模式。
DOI：
10.1073/pnas.86.4.1278
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发表时间：
1989
影响因子：
11.1
通讯作者：
Gordon,JI
中科院分区：
文献类型：
--
作者：
Rubin,DC;Ong,DE;Gordon,JI
我们检查了妊娠第 17 天至第 21 天期间胎鼠小肠上皮的分化模式。在晚期胎儿、新生儿和成人肠细胞中表达的五个基因被用作分化标记。它们编码三种同源的小细胞质疏水配体结合蛋白——肝脂肪酸结合蛋白（L-FABP）、肠脂肪酸结合蛋白（I-FABP）和细胞视黄醇结合蛋白II（CRBP II）——以及两种载脂蛋白——apoAI和apoAIV。 RNA印迹杂交研究表明，从近端小肠到结肠的mRNA浓度梯度似乎与快速上皮细胞增殖和绒毛形成的开始（22天妊娠期的第17-19天）一致。免疫细胞化学研究揭示了三种疏水性配体结合蛋白的细胞特异性表达的显着异质性模式，这在apoAIV或apoAI中并不明显。在 17 至 18 天的胎儿中，在形态相似的细胞中观察到这种“马赛克”染色模式，这些细胞沿着新生绒毛占据相同的地形位置。近端小肠中 I-FABP、L-FABP 和 CRBP II 之间这种嵌合现象的发生和消退有所不同，尽管它在出生后第一天就完全消退了。远端小肠在出现这种初始基因表达的异质模式时表现出 1-2 天的发育延迟。使用 L-FABP 和 I-FABP 抗体的双标记免疫荧光分析表明，在妊娠第 18 天，近端小肠柱状上皮含有多个不表达一种蛋白、一种或两种蛋白的肠细胞群。根据最近对转基因和嵌合小鼠的研究，讨论了肠上皮分化的这种镶嵌模式的潜在意义。
We have examined the pattern of differentiation of the small intestinal epithelium in fetal rats during the 17th through 21st days of gestation. Five genes expressed in late fetal, neonatal, and adult enterocytes were used as markers of differentiation. They encode three homologous small cytoplasmic hydrophobic ligand binding proteins--liver fatty acid binding protein (L-FABP), intestinal fatty acid binding protein (I-FABP), and cellular retinol binding protein II (CRBP II)--and two apolipoproteins--apoAI and apoAIV. RNA blot hybridization studies indicated that gradients in mRNA concentration from the proximal small intestine to colon appear coincident with the initiation of rapid epithelial cell proliferation and villus formation (days 17-19 of the 22-day gestation period). Immunocytochemical studies disclosed a remarkably heterogeneous pattern of cell-specific expression of the three hydrophobic ligand binding proteins that was not apparent with either apoAIV or apoAI. This "mosaic" staining pattern was observed in morphologically similar cells occupying identical topographic positions along nascent villi in 17- to 18-day fetuses. The onset and resolution of this mosaicism varies between I-FABP, L-FABP, and CRBP II in the proximal small bowel, although it completely resolves by the first postnatal day. The distal small intestine exhibits a developmental delay of 1-2 days in the appearance of this heterogeneous pattern of initial gene expression. Double-label immunofluorescent analyses using L-FABP and I-FABP antibodies indicated that on the 18th day of gestation the proximal small intestinal columnar epithelium contains several populations of enterocytes expressing neither, one, or both proteins. The potential significance of this mosaic pattern of intestinal epithelial differentiation is discussed in light of recent studies with transgenic and chimeric mice.