大腦皮層是大腦最大最復(fù)雜的組成部分，哺乳動(dòng)物——尤其是人類,，具有高度發(fā)達(dá)的大腦皮層,。雖然已知組成大腦皮層的神經(jīng)元最初都是由干細(xì)胞分化而來，并且不可逆地形成大腦皮層各個(gè)不同區(qū)域,，但干細(xì)胞分化成各類神經(jīng)元的機(jī)制一直是科學(xué)界還未解開的謎團(tuán),。
索爾克生物研究所的科學(xué)家在一篇發(fā)表于10月11日Nature Neuroscience雜志上，首次發(fā)現(xiàn)關(guān)于上述問題的遺傳機(jī)制,。他們發(fā)現(xiàn),，LIM同源結(jié)構(gòu)域轉(zhuǎn)錄因子Lhx2(LIM homeodomain transcription factor Lhx2 )在某一關(guān)鍵期能夠決定干細(xì)胞分化的命運(yùn)。
胚胎時(shí)期的大腦發(fā)育經(jīng)歷著不同的階段：從萬能干細(xì)胞(omnipotent stem cells)到大腦皮層祖細(xì)胞(cortical progenitor cells),，最終分化為不同的功能區(qū),。在神經(jīng)形成(neurogenesis)早期，神經(jīng)上皮細(xì)胞(neuroepithelial cells)通過對(duì)稱分裂,，形成神經(jīng)上皮細(xì)胞庫,，然后分化為放射狀膠質(zhì)細(xì)胞(radial glia)，該細(xì)胞分化形成的神經(jīng)元組成大腦各個(gè)功能區(qū)的灰質(zhì)(gray matter),。
之前有研究發(fā)現(xiàn)生長因子Fgf10控制著神經(jīng)上皮細(xì)胞向放射狀膠質(zhì)細(xì)胞的分化時(shí)間,。而在接下去的分化方向上,，研究人員猜測(cè)，同源結(jié)構(gòu)域轉(zhuǎn)錄因子Lhx2起著重要的作用,。為了驗(yàn)證該假設(shè),，研究人員在老鼠胚胎干細(xì)胞不同發(fā)育階段剔除Lhx2。
研究發(fā)現(xiàn),，當(dāng)神經(jīng)上皮細(xì)胞分化為放射狀膠質(zhì)細(xì)胞過程中剔除Lhx2,，新大腦皮層轉(zhuǎn)化為嗅覺皮層。而比上述試驗(yàn)晚一天進(jìn)行的試驗(yàn)中,，并未出現(xiàn)上述轉(zhuǎn)化結(jié)果,。該研究結(jié)果表明，Lhx2控制著干細(xì)胞向嗅覺皮層的方向分化,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Neuroscience 11 October 2009 | doi:10.1038/nn.2427
Lhx2 specifies regional fate in Emx1 lineage of telencephalic progenitors generating cerebral cortex
Shen-Ju Chou1, Carlos G Perez-Garcia1, Todd T Kroll1 & Dennis D M O'Leary1
Cerebral cortex is comprised of regions, including six-layer neocortex and three-layer olfactory cortex, generated by telencephalic progenitors of an Emx1 lineage. The mechanism specifying region-specific subpopulations in this lineage is unknown. We found that the LIM homeodomain transcription factor Lhx2 in mice, expressed in graded levels by progenitors, determines their regional identity and fate decisions to generate neocortex or olfactory cortex. Deletion of Lhx2 with Emx1-cre at embryonic day 10.5 (E10.5) altered the fates of progenitors, causing them to generate three-layer cortex, phenocopying olfactory cortex rather than lateral neocortex. Progenitors did not generate ectopic olfactory cortex following Lhx2 deletion at E11.5. Thus, Lhx2 regulates a regional-fate decision by telencephalic progenitors during a critical period that ends as they differentiate from neuroepithelial cells to neuronogenic radial glia. These findings establish a genetic mechanism for determining regional-fate in the Emx1 lineage of telencephalic progenitors that generate cerebral cortex.
1 Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California, USA.
