ACCUMULATION OF COMPONENTS OF BASAL LAMINAE - ASSOCIATION WITH THE FAILURE OF NEURAL CREST CELLS TO COLONIZE THE PRESUMPTIVE AGANGLIONIC BOWEL OF IS/IS MUTANT MICE
ACCUMULATION OF COMPONENTS OF BASAL LAMINAE - ASSOCIATION WITH THE FAILURE OF NEURAL CREST CELLS TO COLONIZE THE PRESUMPTIVE AGANGLIONIC BOWEL OF IS/IS MUTANT MICE
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DOI：
10.1016/0012-1606(88)90217-5
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发表时间：
1988-02-01
影响因子：
2.7
通讯作者：
GERSHON, MD
中科院分区：
文献类型：
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作者：
PAYETTE, RF;TENNYSON, VM;GERSHON, MD
无神经节细胞症发生在ls/ls小鼠的末端结肠中，因为假定的无神经节细胞组织的内在缺陷阻止了迁移的神经嵴细胞进入和定植肠的该部分。目前的研究是为了确定细胞外基质的异常，可以确定在这段可能占迁移失败。由于粘膜肌层的基底层在成年LS/LS小鼠的无神经节段中过度产生，我们检查了妊娠第E11天至第E16天胎儿肠道中的基底层成分。这一时期跨越了肠神经节形成的时间。层粘连蛋白和IV型胶原通过免疫细胞化学和蛋白多糖通过糖胺聚糖与阿尔新蓝染色进行了研究。这些组分中的每一种的缺失发生在ls/ls小鼠中推定的无神经节肠的发育期间，并且早在E11天就可以检测到。这些缺陷主要包括这些材料的过剩，无论是在定义的基底层和整个细胞外间隙的间充质。在假定的无神经节的ls/ls结肠的电子显微镜观察显示，增厚的基底层和异常宽的平滑肌成肌细胞之间的细胞间隙，其中包含一个不规则的纤维状材料，由4.5- 6.0-nm的细丝与14- 20-nm的颗粒。原纤维和絮凝剂材料是连续的形成的基底层，并集中在同一地区发现有一个过度的层粘连蛋白免疫反应。这些观察结果表明，存在细胞外基质材料的积累，包括基底层的组分，其（i）先于肠神经节的形成，（ii）在来自嵴的肠神经前体必须迁移的路径中，以及（iii）限于无神经节的ls/ls肠。这些数据是一致的假设，即基底层的组件导致嵴细胞无法定殖终末肠的LS/LS小鼠。
Aganglionosis occurs in the terminal colon of the ls/ls mouse because an intrinsic defect of the presumptive aganglionic tissue prevents the entry and colonization of this portion of the bowel by migrating neural crest cells. The current study was undertaken to determine if abnormalities of the extracellular matrix could be identified in this segment that might account for migratory failure. Since basal lamina of the muscularis mucosa are overproduced in the aganglionic segment of adult ls/ls mice, we examined components of basal laminae in fetal gut from Day E 11 to Day E 16 of gestation. This period spans the time of enteric ganglion formation. Laminin and collagen type IV were studied by immunocytochemistry and proteoglycans by staining glycosaminoglycans with Alcian blue. Abnormalities of each of these components occur during development of the presumptive aganglionic bowel in the ls/ls mouse and could be detected as early as Day E 11. These defects consist mainly of an overabundance of these materials, both in defined basal laminae and throughout the extracellular space of the mesenchyme. Electron microscopic observations in the presumptive aganglionic ls/ls colon revealed a thickening of basal laminae and exceptionally wide intercellular spaces between smooth muscle myoblasts that contained an irregular fibrillar material, consisting of 4.5- to 6.0-nm filaments associated with 14- to 20-nm granules. Fibrillar and flocculant material was continuous with formed basal laminae, and was concentrated in the same areas found to have an overabundance of laminin immunoreactivity. These observations indicate that there is an accumulation of extracellular matrix material, including components of basal laminae, that (i) precedes the formation of enteric ganglia, (ii) is in the path through which enteric neural precursors from the crest would have to migrate, and (iii) is limited to the aganglionic ls/ls bowel. These data are consistent with the hypothesis that components of basal laminae contribute to the inability of crest cells to colonize the terminal bowel of ls/ls mice.