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Study on the role of epidermal growth factor receptor and protooncogenes in mammalian morphogenesis

表皮生长因子受体和原癌基因在哺乳动物形态发生中的作用研究

基本信息

批准号：
04670014
负责人：
SHIOTA Kohei
金额：
$ 1.41万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

1. Expression and localization of epidermal growth factor receptor (EGF-R)in human embryonic tissuesHuman embryos of 3-8 weeks of gestation were immersion-fixed in 4% paraformaldehyde, embedded in paraffin, and serially sectioned. They were immunostained with anti-rabbit EGF-R antibody and examined after diaminobenzidine/H_2O_2 reaction. Characteristic tissue-specific localization of EGF-R was noted, and the epithelia of the digestive tube and respiratory tract, cartilage, kidney, and epidermis were strongly positive for the reactive products against EGF-R.Proliferating epithelial tissues were selectively reactive, suggesting that epidermal growth factor may play a key role in the proliferation and differentiation of epithelial tissues in human embryos.2. Expression of EGF-R in the fusing palatal shelves of mouse fetuses.Expression of EGF-R was examined immunohistochemically in the palates of days-12-14 mouse fetuses. Immunoreactive products against EGF-R was detected in palatal epithelia as well as underlying mesenchyme, and spatial heterogeneity and temporal sequence were noted which arppeared closely related to the palatogenetic process.3. Expression of EGF-R in dysmorphogenesisCleft Palate is frequently produced if pregnant female mice are treated with retinoic acid. Pregnant female mice were given orally 80-100 mg/kg all-trans retinoic acid and their fetuses were examined immurnohistochemically for EGF-R.The expression of EGF-R in the palatal tissue of treated fetuses were significantly more intense than in the corresponding tissue of control fetuses. It seems that retinoic acid disturbs the normal regulation of EGF-R expression and thereby inhibit the fusion of palatal shelves.The present study has shown that epidermal growth factor and related protooncogenes may play important role in mammalian morphogenesis.

1.表皮生长因子受体（EGF-R）在人胚胎组织中的表达与定位取孕3-8周的人胚胎，用4%多聚甲醛固定，石蜡包埋，连续切片。用抗兔EGF-R抗体进行免疫组化染色，经二氨基联苯胺/H_2O_2反应后检测。EGF-R具有组织特异性定位，消化道、呼吸道上皮、软骨、肾脏和表皮均呈强阳性反应，对人胚胎上皮组织呈选择性反应，提示表皮生长因子可能在人胚胎上皮组织的增殖和分化中起关键作用. EGF-R在小鼠胚胎腭突融合过程中的表达：应用免疫组化方法检测了12-14天小鼠胚胎腭突中EGF-R的表达。EGF-R免疫反应产物在腭上皮及间充质中均有表达，并存在空间异质性和时间序列性，与腭发育过程密切相关. EGF-R在畸形发生中的表达如果用维甲酸处理怀孕的雌性小鼠，经常会产生腭裂。孕鼠经口给予80-100 mg/kg全反式维甲酸，用免疫组化方法检测胎鼠的EGF-R表达，结果显示，给药组胎鼠腭部组织EGF-R表达明显强于对照组胎鼠相应组织。研究表明，表皮生长因子及其相关原癌基因可能在哺乳动物的形态发生中起重要作用。