Epigenetic role of epidermal growth factor expression and signalling in embryonic mouse lung morphogenesis.
Epigenetic role of epidermal growth factor expression and signalling in embryonic mouse lung morphogenesis.
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表皮生长因子表达和信号传导在胚胎小鼠肺形态发生中的表观遗传作用。
DOI：
10.1016/0012-1606(92)90269-m
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发表时间：
1992
影响因子：
2.7
通讯作者：
Slavkin,HC
中科院分区：
文献类型：
--
作者：
Warburton,D;Seth,R;Shum,L;Horcher,PG;Hall,FL;Werb,Z;Slavkin,HC
发育生物学中一个尚未解决的主要问题是确定何时以及如何在次级胚胎诱导（如分支形态发生）期间发出和接收时间和位置限制指令。小鼠胚胎肺的雏形被用来测试的假设，内源性肽生长因子，特别是表皮生长因子（EGF），作为指导性的表观遗传信号的形态发生。采用逆转录酶偶联聚合酶链反应检测E11-E17天小鼠胚胎肺组织和E11天肺组织中EGF前体mRNA转录物的存在。免疫定位确定了一个位置限制分布的EGF和周围的原始气道duringin vivolung形态发生和文化。表皮生长因子受体（EGFR）与EGF共同免疫定位于原始气道。此外，外源性表皮生长因子肺培养导致显着的浓度依赖性刺激的分支形态发生，DNA，RNA和蛋白质含量，并在[3 H]胸苷掺入DNA。相反，tyrphostin（特异性EGF受体激酶拮抗剂）在培养肺导致浓度依赖性抑制分支形态发生，DNA，RNA和蛋白质含量，并在[3 H]胸苷掺入DNA没有明显的细胞毒性。酪氨酸磷酸化蛋白的免疫沉淀证实了酪氨酸磷酸化蛋白对EGF信号的抑制。我们的结论是，早期小鼠胚胎肺表达EGF转录本和相应的EGF肽在一个特定的位置限制的分布coimmunolocalizes与表皮生长因子受体在原始气道，而刺激和抑制的研究表明，肺分支形态发生的表观遗传调控的转导的EGF信号的功能作用。我们推测肽生长因子EGF在次级胚胎形态发生诱导中起作用，这可能是通过与其他生长因子的相互作用来调节的。
A major unsolved problem in developmental biology is to determine when and how time- and position-restricted instructions are signaled and received during secondary embryonic inductions such as branching morphogenesis. The mouse embryonic lung rudiment was used to test the hypothesis that endogenous peptide growth factors, specifically epidermal growth factor (EGF), serve as instructive epigenetic signals for morphogenesis. The presence of EGF precursor mRNA transcripts was detected using the reverse-transcriptase-coupled polymerase chain reaction both in E11-E17-day mouse embryo lung tissuesin vivoand in E11-day lung cultured for up to 7 daysin vitrounder chemically defined, serum-free conditions. Immunolocalization identified a position-restricted distribution of EGF in and around the primitive airways both duringin vivolung morphogenesis and in culture. EGF receptors (EGFR) coimmunolocalized with EGF in the primitive airways. Addition of exogenous EGF to lungs in culture resulted in significant concentration-dependent stimulation of branching morphogenesis, DNA, RNA, and protein content, and in [3H]thymidine incorporation into DNA. Conversely, the addition of tyrphostin (specific EGF receptor kinase antagonist) to lungs in culture resulted in concentration-dependent inhibition of branching morphogenesis, DNA, RNA, and protein content, and in [3H]thymidine incorporation into DNA without apparent cytotoxicity. The inhibition of the EGF signal by tyrphostin was confirmed by immunoprecipitation of tyrosine phosphoproteins. We conclude that early mouse embryo lungs express EGF transcripts and corresponding EGF peptides in a specific position-restricted distribution which coimmunolocalizes with EGFR in the primitive airways, while stimulatory and inhibitory studies indicate a functional role for the transduced EGF signal in the epigenetic regulation of lung branching morphogenesis. We speculate that the peptide growth factor EGF serves a function in secondary embryonic morphogenetic inductions, which may be modulated by interaction with other growth factors.