研究者認為,這一新發(fā)現(xiàn)有望促進先天性巨結(jié)腸發(fā)病機制研究,。
腸神經(jīng)系統(tǒng)是縱貫胃腸消化道的神經(jīng)系統(tǒng),,具有復雜的結(jié)構(gòu),,即使大腦沒有發(fā)出指令,,也能調(diào)節(jié)胃腸消化道的功能,有“第二大腦”之稱,。
日本理化研究所發(fā)育生物學研究中心研究員榎本秀樹領導的小組,,19日在英國期刊《自然—神經(jīng)科學》網(wǎng)絡版上報告說,他們通過改變實驗鼠基因,,使實驗鼠受精卵的腸神經(jīng)前體細胞能夠合成在紫外線照射下改變顏色的熒光蛋白,,再借助活細胞成像技術(shù)進行觀察。
研究人員發(fā)現(xiàn)在卵細胞受精后11天左右,,小腸和大腸的某些部分平行分布時,,會有細胞群“抄近道”橫穿兩者之間的膜從小腸進入大腸,這些細胞成為形成大腸內(nèi)腸神經(jīng)系統(tǒng)的“主力軍”,。
研究人員還發(fā)現(xiàn),,如果細胞無法“抄近道”移動到大腸,就會出現(xiàn)類似先天性巨結(jié)腸的神經(jīng)缺損,。他們認為,,如果能確定細胞群移動時所必需的蛋白質(zhì),就可以了解先天性巨結(jié)腸的發(fā)病機制,。
先天性巨結(jié)腸又稱無神經(jīng)節(jié)細胞癥,,是小兒外科常見的消化道畸形之一?;純簳霈F(xiàn)腸神經(jīng)缺損,,導致腸道的一部分無法發(fā)揮作用。(生物谷Bioon.com)
doi:10.1038/nn.3184
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Trans-mesenteric neural crest cells are the principal source of the colonic enteric nervous system
Chihiro Nishiyama, Toshihiro Uesaka, Takayuki Manabe, Yohei Yonekura, Takashi Nagasawa, Donald F Newgreen, Heather M Young & Hideki Enomoto
Cell migration is fundamental to organogenesis. During development, the enteric neural crest cells (ENCCs) that give rise to the enteric nervous system (ENS) migrate and colonize the entire length of the gut, which undergoes substantial growth and morphological rearrangement. How ENCCs adapt to such changes during migration, however, is not fully understood. Using time-lapse imaging analyses of mouse ENCCs, we show that a population of ENCCs crosses from the midgut to the hindgut via the mesentery during a developmental time period in which these gut regions are transiently juxtaposed, and that such 'trans-mesenteric' ENCCs constitute a large part of the hindgut ENS. This migratory process requires GDNF signaling, and evidence suggests that impaired trans-mesenteric migration of ENCCs may underlie the pathogenesis of Hirschsprung disease (intestinal aganglionosis). The discovery of this trans-mesenteric ENCC population provides a basis for improving our understanding of ENS development and pathogenesis.