Cooperative interactions between extracellular matrix, integrins and parathyroid hormone-related peptide regulate parietal endoderm differentiation in mouse embryos.
Cooperative interactions between extracellular matrix, integrins and parathyroid hormone-related peptide regulate parietal endoderm differentiation in mouse embryos.
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发表时间：
1995-12
期刊：
影响因子：
4.6
通讯作者：
O. Behrendtsen;C. Alexander;Z. Werb
中科院分区：
文献类型：
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作者：
O. Behrendtsen;C. Alexander;Z. Werb
壁内胚层（PE）细胞从前体内胚层细胞的生长是小鼠胚胎中发生的第一个分化事件之一。我们分析了这一过程的分子决定因素，通过将分离的内细胞团（ICM）在微滴培养物中定义的细胞外基质上。PE的分化和生长需要纤维连接蛋白基质。层粘连蛋白支持内脏内胚层（VE）的粘附和生长，并在纤维连接蛋白和层粘连蛋白的混合物中积极抑制PE的分化。IV型胶原蛋白、明胶、玻连蛋白或巢蛋白支持很少或没有内胚层生长。滋养外胚层（TE）细胞在体内PE诱导中具有重要作用。我们发现，与TE细胞或TE细胞条件培养基培养的ICM重组，大大增加了PE的分化。TE细胞刺激PE生长的基质以外的纤维连接蛋白。一种由滋养层和内胚层细胞分泌的细胞因子，甲状旁腺素相关肽（PTHrP），对于任何基质上的生长都是至关重要的。PTHrP的功能干扰抗体减少了PE细胞的数量，而加入PTHrP则增加了该数量。此外，PTHrP的加入改变了生长的基质要求，使得层粘连蛋白、玻连蛋白和低浓度的纤连蛋白允许PE生长。用抗整联蛋白抗体的免疫染色显示，在纤连蛋白上生长的完全分化的PE细胞表达α 5、α 6和α v β 3整联蛋白。然而，在α 5、α 6和α v β 3整联蛋白的功能干扰抗体存在下的产物分析显示，这些整联蛋白分别仅在纤连蛋白、层粘连蛋白和玻连蛋白基质上指导PE产物。我们已经表明，有一个合作的细胞外基质，整合素和PTHrP的相互作用，调节PE的生长。
The outgrowth of parietal endoderm (PE) cells from precursor endodermal cells is one of the first differentiation events that occur in mouse embryos. We have analyzed the molecular determinants of this process by placing isolated inner cell masses (ICMs) on defined extracellular matrix substrata in microdrop cultures. Differentiation and outgrowth of PE required a fibronectin substratum. Laminin supported the adhesion and outgrowth of visceral endoderm (VE) and actively suppressed the differentiation of PE in mixtures of fibronectin and laminin. Collagen type IV, gelatin, vitronectin or entactin supported little or no endodermal outgrowth. Trophectoderm (TE) cells have been implied to be important in PE induction in vivo. We found that recombination of ICMs in culture with TE cells, or with medium conditioned by TE cells, greatly increased the differentiation of PE. TE cells stimulated PE outgrowth on substrata other than fibronectin. One cytokine secreted by trophoblast and endodermal cells, parathyroid hormone-related peptide (PTHrP), was critical for outgrowth on any substratum. A function-perturbing antibody to PTHrP reduced the number of PE cells, whereas the addition of PTHrP increased that number. Furthermore, addition of PTHrP changed the substratum requirements for outgrowth, making laminin, vitronectin and low concentrations of fibronectin permissive for PE outgrowth. Immunostaining with anti-integrin antibodies showed that fully differentiated PE cells outgrowing on fibronectin expressed alpha 5, alpha 6 and alpha v beta 3 integrins. However, analysis of outgrowths in the presence of function-perturbing antibodies to alpha 5, alpha 6 and alpha v beta 3 integrins showed that these integrins directed PE outgrowth only on fibronectin, laminin and vitronectin substrata, respectively. We have shown that there is a cooperative interplay of extracellular matrix, integrins and PTHrP that modulates PE outgrowth.