TIME OF ORIGIN OF NEURONS IN THE MURINE ENTERIC NERVOUS-SYSTEM - SEQUENCE IN RELATION TO PHENOTYPE
TIME OF ORIGIN OF NEURONS IN THE MURINE ENTERIC NERVOUS-SYSTEM - SEQUENCE IN RELATION TO PHENOTYPE
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DOI：
10.1002/cne.903140411
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发表时间：
1991-12-22
影响因子：
2.5
通讯作者：
ROTHMAN, TP
中科院分区：
文献类型：
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作者：
PHAM, TD;GERSHON, MD;ROTHMAN, TP
假设进行了测试，发展肠神经元退出细胞周期的顺序与他们的表型。在小鼠十二指肠和空肠中测定免疫细胞化学鉴定的肌间和粘膜下神经元的诞生日。[H-3]胸苷（[H-3]TdR）在24小时内以4-8小时间隔注射到定时妊娠小鼠或幼仔中。在出生后第30天（P30）处死幼仔。用放射自显影法检测肠神经元[H-3]TdR掺入，同时检测5-羟色胺（5-HT）、胆碱乙酰转移酶（ChAT）、神经肽Y（NPY）、脑啡肽（ENK）、降钙素基因相关肽（CGRP）和血管活性肠肽（VIP）的免疫反应性，进行表型鉴定。确定含有这些标记物的神经元最早从细胞周期中退出的日期，以及所识别的神经元继续出生的时间长度，以及它们的出生率最大的日期。含有5-HT（E8-E14，E10时达到峰值）或ChAT（E8-E15，E12时达到峰值）的肌间神经元的出生日期往往早于含有ENK（E10-E18，E14时达到峰值）、NPY（E10-E18，E15时达到峰值）、VIP（E10-P5，E15时达到峰值）或CGRP（E10-P3，E17时达到峰值）的肌间神经元。对于任何给定的免疫细胞化学定义的神经元表型，粘膜下神经元往往出生晚于他们的肌间对应和粘膜下神经元，含有神经肽出生晚于那些只含有ChAT免疫反应。第一个5-HT-和ChAT-免疫反应性神经元成为有丝分裂后的一天（E8）早于已检测到肠嵴衍生细胞定植的一天（E9）。因此，定居在肠道的神经前体细胞群是异质的;许多细胞正在增殖，但最终将产生胆碱能或胆碱能神经元的特定子集已经处于有丝分裂后。神经元在整个胎儿期甚至在出生后继续生成。因此，终末分化的神经元与分裂的神经前体细胞共存于发育中的肠神经系统中。这一观察结果与早期发育的神经元可能影响肠神经前体的发育的想法一致;此外，他们还证明，即使在肠道所依赖的神经回路已经发挥作用之后，也有可能将神经元添加到肠神经丛中。
The hypothesis was tested that developing enteric neurons withdraw from the cell cycle in a sequence related to their phenotype. The birthdays of immunocytochemically identified myenteric and submucosal neurons were determined in the murine duodenum and jejunum. [H-3]thymidine ([H-3]TdR) was injected into timed pregnant mice or pups at 4-8 hour intervals over a 24 hour period. Pups were killed on postnatal day 30 (P30). [H-3]TdR incorporation was detected by radioautography in enteric neurons, which were phenotypically identified by the simultaneous detection of the immunoreactivities of 5-hydroxytryptamine (5-HT), choline acetyl transferase (ChAT), neuropeptide Y (NPY), enkephalin (ENK), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP). The dates of the earliest withdrawal from the cell cycle of neurons containing these markers were determined, as well as the length of time during which the identified neurons continued to be born, and the date on which their rate of birth was maximal. The birthdates of myenteric neurons that contained 5-HT (E8-E14, peak at E10) or ChAT (E8-E15, peak at E12) tended to be earlier than those that contained ENK (E10-E18, peak at E14), NPY (E10-E18, peak at E15), VIP (E10-P5, peak at E15), or CGRP (E10-P3, peak at E17). For any given immunocytochemically defined neuronal phenotype, submucosal neurons tended to be born later than their myenteric counterparts and submucosal neurons that contained neuropeptides were born later than those that contained only ChAT immunoreactivity. The day (E8) on which the first 5-HT- and ChAT-immunoreactive neurons became postmitotic is earlier than the day (E9) on which the colonization of the bowel by crest-derived cells has been detected. The population of neural precursors that colonizes the gut, therefore, is heterogeneous; many cells are proliferating, but a specific subset, which will ultimately give rise to serotoninergic or cholinergic neurons, is already postmitotic. Neurons continued to be born throughout fetal life and even after birth. Consequently, terminally differentiated neurons coexist in the developing enteric nervous system with dividing neural precursor cells. This observation is consistent with the idea that early developing neurons could affect the development of enteric neural precursors; moreover, they also demonstrate that it is possible to add neurons to the enteric plexuses even after the neural circuits on which the bowel depends have become functional.