2012年4月16日,，科羅拉多大學(xué)醫(yī)學(xué)院的研究人員發(fā)現(xiàn)，缺乏一種特定基因可中斷神經(jīng)管閉合，神經(jīng)管閉合中斷可導(dǎo)致死亡或癱瘓。
神經(jīng)管(英文：neuraltube)為脊椎動物及原索動物的神經(jīng)胚期所見到的一種最明顯的變化,，神經(jīng)板閉合作為中樞神經(jīng)系統(tǒng)最初原基的神經(jīng)管形成過程的總稱。其中也包含著伴隨形態(tài)形成活動,、神經(jīng)母細胞等出現(xiàn)的神經(jīng)上皮分化過程,。這項研究的主要領(lǐng)導(dǎo)者Lee Niswander博士說：mLin41基因的缺陷阻斷管神經(jīng)管閉合,，因為沒有足夠的神經(jīng)祖細胞產(chǎn)生,，相關(guān)論文發(fā)表在雜志Genes＆Development上。
Niswander和論文的第一作者Jianfu Chen博士等人研究了小鼠神經(jīng)干細胞,。他們認為這些細胞在胚胎發(fā)育的不同階段使用不同的自我更新程序,，以滿足組織的生長和修復(fù)的需求。但調(diào)控這些程序的分子機制仍未知,。
研究人員發(fā)現(xiàn),，小鼠mLin41基因在神經(jīng)閉合過程中，而不是在大腦發(fā)育后期階段控制神經(jīng)干細胞的增殖程度,。
據(jù)Chen描述：有關(guān)神經(jīng)管形成連接方面,，小分子RNAs和RNA的調(diào)控因子從來沒有被研究過。
Niswander是總部設(shè)在華盛頓的霍華德·休斯醫(yī)學(xué)研究所的研究員,。（生物谷：Bioon.com）
doi:10.1101/gad.187641.112 Genes & Dev. 2012. 26: 803-815
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The ubiquitin ligase mLin41 temporally promotes neural progenitor cell maintenance through FGF signaling
Jianfu Chen, Fan Lai and Lee Niswander
How self-renewal versus differentiation of neural progenitor cells is temporally controlled during early development remains ill-defined. We show that mouse Lin41 (mLin41) is highly expressed in neural progenitor cells and its expression declines during neural differentiation. Loss of mLin41 function in mice causes reduced proliferation and premature differentiation of embryonic neural progenitor cells. mLin41 was recently implicated as the E3 ubiquitin ligase that mediates degradation of Argonaute 2 (AGO2), a key effector of the microRNA pathway. However, our mechanistic studies of neural progenitor cells indicate mLin41 is not required for AGO2 ubiquitination or stability. Instead, mLin41-deficient neural progenitors exhibit hyposensitivity for fibroblast growth factor (FGF) signaling. We show that mLin41 promotes FGF signaling by directly binding to and enhancing the stability of Shc SH2-binding protein 1 (SHCBP1) and that SHCBP1 is an important component of FGF signaling in neural progenitor cells. Thus, mLin41 acts as a temporal regulator to promote neural progenitor cell maintenance, not via the regulation of AGO2 stability, but through FGF signaling.
