Fetal endoderm primarily holds the temporal and positional information required for mammalian intestinal development.
Fetal endoderm primarily holds the temporal and positional information required for mammalian intestinal development.
复制标题
DOI：
10.1083/jcb.126.1.211
复制
发表时间：
1994-07
影响因子：
7.8
通讯作者：
Kedinger, M
中科院分区：
文献类型：
--
作者：
Duluc, I;Freund, J N;Leberquier, C;Kedinger, M
在啮齿类动物中，肠道在出生后发育过程中逐渐获得功能区域化。使用乳糖酶根皮苷水解酶作为标记，我们分析了在异种移植模型的个体发育潜能的胚胎大鼠肠段采取前内胚层细胞分化。从假定的近端空肠和远端回肠移植到裸鼠的片段开发了正确的乳糖酶蛋白和mRNA表达的空间和时间模式，再现了正常的断奶前和断奶后的条件。鸡胚移植后8-10 d，胚胎结肠段显示微弱的乳糖酶免疫染色，但小鼠中没有;这与新生大鼠结肠中该酶的瞬时表达一致。异位交叉协会，包括内胚层和间充质从假定的近端空肠和远端回肠发展为异种移植在裸鼠，他们表现出乳糖酶mRNA和蛋白质的表达模式，是典型的起源的内胚层部分。当与胎儿皮肤成纤维细胞相关联时，来自回肠远端的内胚层也表达正常的乳糖酶模式，而成纤维细胞分化成含有α-平滑肌肌动蛋白的肌肉层。值得注意的是，包括结肠内胚层和小肠间充质的协会表现出典型的小肠形态，并表达了消化酶蔗糖酶-异麦芽糖酶通常不存在于结肠。然而，在包括肺或胃内胚层和小肠间质的异源协会中，上皮隔室根据其组织来源表达标记物，但既不是肠乳糖酶也不是蔗糖酶-异麦芽糖酶。移植物周围有一层厚厚的肠肌被，其中细胞表达α-平滑肌肌动蛋白。结果表明：（a）直到断奶后阶段的肠个体发育所需的时间和位置信息来自于内胚层细胞分化之前在哺乳动物胎儿中固定的内在程序;（B）该时间和位置信息主要由内胚层部分携带，该内胚层部分也能够改变异源中胚层细胞的命运以形成肠间充质;和（c）小肠间充质反过来可以传递与结肠内胚层相关的指导性信息;然而，这种作用在非肠内胚层中不明显。
In rodents, the intestinal tract progressively acquires a functional regionalization during postnatal development. Using lactase-phlorizin hydrolase as a marker, we have analyzed in a xenograft model the ontogenic potencies of fetal rat intestinal segments taken prior to endoderm cytodifferentiation. Segments from the presumptive proximal jejunum and distal ileum grafted in nude mice developed correct spatial and temporal patterns of lactase protein and mRNA expression, which reproduced the normal pre- and post-weaning conditions. Segments from the fetal colon showed a faint lactase immunostaining 8-10 d after transplantation in chick embryos but not in mice; it is consistent with the transient expression of this enzyme in the colon of rat neonates. Heterotopic cross-associations comprising endoderm and mesenchyme from the presumptive proximal jejunum and distal ileum developed as xenografts in nude mice, and they exhibited lactase mRNA and protein expression patterns that were typical of the origin of the endodermal moiety. Endoderm from the distal ileum also expressed a normal lactase pattern when it was associated to fetal skin fibroblasts, while the fibroblasts differentiated into muscle layers containing alpha-smooth- muscle actin. Noteworthy, associations comprising colon endoderm and small intestinal mesenchyme showed a typical small intestinal morphology and expressed the digestive enzyme sucrase-isomaltase normally absent in the colon. However, in heterologous associations comprising lung or stomach endoderm and small intestinal mesenchyme, the epithelial compartment expressed markers in accordance to their tissue of origin but neither intestinal lactase nor sucrase-isomaltase. A thick intestinal muscle coat in which cells expressed alpha-smooth- muscle actin surrounded the grafts. The results demonstrate that: (a) the temporal and positional information needed for intestinal ontogeny up to the post-weaning stage results from an intrinsic program that is fixed in mammalian fetuses prior to endoderm cytodifferentiation; (b) this temporal and positional information is primarily carried by the endodermal moiety which is also able to change the fate of heterologous mesodermal cells to form intestinal mesenchyme; and (c) the small intestinal mesenchyme in turn may deliver instructive information as shown in association with colonic endoderm; yet this effect is not obvious with nonintestinal endoderms.