Filamin A mediated Big2 dependent endocytosis: From apical abscission to periventricular heterotopia.
Filamin A mediated Big2 dependent endocytosis: From apical abscission to periventricular heterotopia.
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DOI：
10.4161/tisb.29431
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发表时间：
2014
期刊：
影响因子：
3.1
通讯作者：
Sheen VL
中科院分区：
文献类型：
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作者：
Sheen VL
脑室周围异位症(PH)是最常见的皮质发育畸形之一。侧脑室结节、脑室衬里破裂和脑体积缩小是这种疾病的特征。PH会导致神经室管膜的破坏，抑制神经的增殖和分化，并改变神经元的迁移。人类编码肌动蛋白结合丝蛋白A(Flna)和囊泡运输蛋白Brefeldin A相关的鸟嘌呤交换因子2(BIG2由ARFGEF2基因编码)的基因突变与PH的形成有关。最近的研究表明，从增殖的神经前体细胞向有丝分裂后神经元的转变依赖于神经上皮细胞的顶端脱落。这种机制包括依赖肌动蛋白的神经前体细胞的顶端部分沿着脑室内壁收缩，以完成脱落。肌动蛋白还维持神经室管膜上各种细胞黏附分子的稳定性。钙粘附素的丢失指导初级纤毛的分解，初级纤毛转导声波-刺猬(Shh)信号。ShH信号是持续增殖所必需的。在这种情况下，顶端脱落通过从神经室管膜分离来调节神经前体细胞退出和迁移到脑室区域，依赖于维持神经上皮细胞衬里完整性的黏附分子，并指导神经增殖。在PH中，这些过程中的每一个都被破坏，这表明导致这种MCD的基因可能从根本上介导了皮质发育中的顶端脱落。在这里，我们讨论了几个最近的报告，这些报告表明肌动蛋白和囊泡运输在调节神经上皮细胞的神经发育以及潜在的神经干细胞到神经元的转变中起着协调作用。
Periventricular heterotopia (PH) is one of the most common malformations of cortical development (MCD). Nodules along the lateral ventricles of the brain, disruption of the ventricular lining, and a reduced brain size are hallmarks of this disorder. PH results in a disruption of the neuroependyma, inhibition of neural proliferation and differentiation, and altered neuronal migration. Human mutations in the genes encoding the actin-binding Filamin A (FLNA) and the vesicle trafficking Brefeldin A-associated guanine exchange factor 2 (BIG2 is encoded by the ARFGEF2 gene) proteins are implicated in PH formation. Recent studies have shown that the transition from proliferating neural progenitors to post-mitotic neurons relies on apical abscission along the neuroepithelium. This mechanism involves an actin dependent contraction of the apical portion of a neural progenitor along the ventricular lining to complete abscission. Actin also maintains stability of various cell adhesion molecules along the neuroependyma. Loss of cadherin directs disassembly of the primary cilium, which transduces sonic-hedgehog (Shh) signaling. Shh signaling is required for continued proliferation. In this context, apical abscission regulates neuronal progenitor exit and migration from the ventricular zone by detachment from the neuroependyma, relies on adhesion molecules that maintain the integrity of the neuroepithelial lining, and directs neural proliferation. Each of these processes is disrupted in PH, suggesting that genes causal for this MCD, may fundamentally mediate apical abscission in cortical development. Here we discuss several recent reports that demonstrate a coordinated role for actin and vesicle trafficking in modulating neural development along the neurepithelium, and potentially the neural stem cell to neuronal transition.