Cell Reports:奥科学家发现影响大脑发育关键基因

2012-12-18 Cell Reports Cell Reports

       在最新的《细胞报告》杂志网络版上,奥地利维也纳分子病理学研究所科学家12月13日发表报告称,该研究所发现了影响人类大脑发育的一个关键基因,这种基因的突变会导致严重的大脑发育障碍。   报告称,目前全世界新生儿中患有病理性头小畸形的约占万分之一,由于大脑发育缺陷,患者的寿命通常不长。医学界认为,除酗酒、受到过量辐射以及孕期风疹等病毒感染


       在最新的《细胞报告》杂志网络版上,奥地利维也纳分子病理学研究所科学家12月13日发表报告称,该研究所发现了影响人类大脑发育的一个关键基因,这种基因的突变会导致严重的大脑发育障碍。

  报告称,目前全世界新生儿中患有病理性头小畸形的约占万分之一,由于大脑发育缺陷,患者的寿命通常不长。医学界认为,除酗酒、受到过量辐射以及孕期风疹等病毒感染因素外,基因缺陷更可能导致婴儿的大脑发育缺陷。

  生物学家戴维·凯斯领导的研究小组在实验鼠实验中发现,一种名为“TUBB5”的基因变异会导致胎儿头小畸形。这种基因变异可引起微管蛋白异常,微管蛋白是细胞内微管的基本结构单位,在细胞的运动和分裂中都发挥着重要作用。他们也在头小畸形患者身上发现了变异的“TUBB5”基因。

  戴维·凯斯认为,了解“TUBB5”基因是通向解开人类大脑发育之谜的一个重要环节,为有朝一日可能找到医治相关疾病的办法奠定了基础。



Highlights
The β-tubulin Tubb5 is highly expressed in the developing mouse and human cortex
In vivo knockdown of Tubb5 perturbs the cell cycle and alters neuronal positioning
Mutations in TUBB5 cause microcephaly with dysmorphic basal ganglia in humans
TUBB5 mutations affect chaperone-mediated tubulin folding in different ways
Summary
The formation of the mammalian cortex requires the generation, migration, and differentiation of neurons. The vital role that the microtubule cytoskeleton plays in these cellular processes is reflected by the discovery that mutations in various tubulin isotypes cause different neurodevelopmental diseases, including lissencephaly (TUBA1A), polymicrogyria (TUBA1A, TUBB2B, TUBB3), and an ocular motility disorder (TUBB3). Here, we show that Tubb5 is expressed in neurogenic progenitors in the mouse and that its depletion in vivo perturbs the cell cycle of progenitors and alters the position of migrating neurons. We report the occurrence of three microcephalic patients with structural brain abnormalities harboring de novo mutations in TUBB5 (M299V, V353I, and E401K). These mutant proteins, which affect the chaperone-dependent assembly of tubulin heterodimers in different ways, disrupt neurogenic division and/or migration in vivo. Our results provide insight into the functional repertoire of the tubulin gene family, specifically implicating TUBB5 in embryonic neurogenesis and microcephaly.

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    2013-08-19 维他命
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    2012-12-19 neurowu
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