有關小鼠的唾液腺是如何發(fā)育的新的發(fā)現(xiàn)可能為頭頸部接觸放射線的癌癥病人的這些腺體的再生帶來新的方法,。研究論文9月24日在線發(fā)表于《科學》雜志上,。
大多數(shù)人對神經(jīng)活動控制著唾液腺功能的概念是熟悉的,這一概念可回溯到巴甫洛夫的經(jīng)典實驗,;在這些實驗中,,巴甫洛夫通過條件反射將狗的唾液分泌與鈴聲聯(lián)系在了一起。 如今,,在一個世紀之后,,由Sarah Knox及其同事所開展的研究證明,神經(jīng)對唾液產(chǎn)生的影響要比人們預計的早的多,,這種影響甚至在胚胎發(fā)育期就已經(jīng)存在,。
像其他的器官一樣,唾液腺發(fā)育是通過一種在上皮細胞與周邊細胞之間的信號傳遞來精細調節(jié)新生腺體萌芽的生長過程而進行的,。 在腺體新萌芽剛出現(xiàn)的一天之后,,被稱作神經(jīng)節(jié)的神經(jīng)組織就致密地圍繞著這些萌芽。 研究人員如今報告,,這些神經(jīng)的信號傳導活動保護著一種上皮祖細胞種群,,這些祖細胞可以產(chǎn)生出新的腺體細胞,而這種腺體細胞會在成人的腺體中得到維持,。 在發(fā)育的前列腺中也是以一種類似的系統(tǒng)運作的,。
在一則相關的觀點欄目中,Jason Rock 和 Brigid Hogan指出,,對頭頸部腫瘤進行放射療法的一個副作用是對唾液腺的無法挽救的損害,,從而引起患者的口腔干燥癥。這是一種對病人生活品質造成嚴重損害的情況,,而目前這種疾病是無法治愈的,。
他們提出,研究人員可能會在將來某一天通過在局部施予可促進神經(jīng)膠質細胞信號傳導(類似Knox及其同事所描述的)的藥物或通過促進激神經(jīng)膠質細胞的生長來刺激唾液腺的再生,。
原文摘要:
Science DOI: 10.1126/science.1192046
Parasympathetic Innervation Maintains Epithelial Progenitor Cells During Salivary Organogenesis
S. M. Knox,1 I. M. A. Lombaert,1 X. Reed,1 L. Vitale-Cross,2 J. S. Gutkind,2 M. P. Hoffman1,*
The maintenance of a progenitor cell population as a reservoir of undifferentiated cells is required for organ development and regeneration. However, the mechanisms by which epithelial progenitor cells are maintained during organogenesis are poorly understood. We report that removal of the parasympathetic ganglion in mouse explant organ culture decreased the number and morphogenesis of keratin 5–positive epithelial progenitor cells. These effects were rescued with an acetylcholine analog. We demonstrate that acetylcholine signaling, via the muscarinic M1 receptor and epidermal growth factor receptor, increased epithelial morphogenesis and proliferation of the keratin 5–positive progenitor cells. Parasympathetic innervation maintained the epithelial progenitor cell population in an undifferentiated state, which was required for organogenesis. This mechanism for epithelial progenitor cell maintenance may be targeted for organ repair or regeneration.
1 Matrix and Morphogenesis Unit, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, NIH, 30 Convent Drive, Bethesda, MD 20892, USA.
2 Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, NIH, 30 Convent Drive, Bethesda, MD 20892, USA