Tsai Jin-Wu, Bremner K Helen, Vallee Richard B
Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University, 630 W 168th Street, New York, New York 10032, USA.
Nat Neurosci. 2007 Aug;10(8):970-9. doi: 10.1038/nn1934. Epub 2007 Jul 8.
During brain development, neural precursor cells migrate along radial glial fibers to populate the neocortex. RNA interference (RNAi) of the lissencephaly gene LIS1 (also known as PAFAH1b1) inhibits somal movement but not process extension of neural precursors in live brain slices. Here we report imaging of the subcellular events accompanying neural precursor migration and the effects of LIS1, cytoplasmic dynein and myosin II inhibition. Centrosomes move continuously and often far in advance of nuclei, which show extreme saltatory behavior. LIS1 and dynein RNAi inhibit centrosomal and nuclear movement independently, whereas myosin II inhibition blocks only nuclear translocation. Imaging of the microtubule end-binding protein 3 (EB3) reveals a centrosome-centered array of microtubules in live neural precursors under all conditions examined. Dynein is concentrated both at a swelling in the leading process reported to initiate each migratory cycle and in the soma. Thus, dynein pulls on the microtubule network from the swelling. The nucleus is transported along the trailing microtubules by dynein assisted by myosin II.
在大脑发育过程中，神经前体细胞沿着放射状胶质纤维迁移，以填充新皮层。无脑回畸形基因LIS1（也称为PAFAH1b1）的RNA干扰（RNAi）可抑制活体脑片中神经前体细胞的胞体移动，但不影响其突起延伸。在此，我们报告了伴随神经前体细胞迁移的亚细胞事件成像以及LIS1、胞质动力蛋白和肌球蛋白II抑制的影响。中心体持续移动，且常常在细胞核之前移动很远的距离，而细胞核表现出极端的跳跃行为。LIS1和动力蛋白RNAi分别独立抑制中心体和细胞核的移动，而肌球蛋白II抑制仅阻断细胞核的易位。对微管末端结合蛋白3（EB3）的成像显示，在所有检测条件下，活体神经前体细胞中均存在以中心体为中心的微管阵列。动力蛋白集中于据报道启动每个迁移周期的前端突起的肿胀处以及胞体中。因此，动力蛋白从肿胀处拉动微管网络。细胞核在肌球蛋白II的协助下，由动力蛋白沿着后端微管运输。
