Gap junctions modulate interkinetic nuclear movement in retinal progenitor cells
Gap junctions modulate interkinetic nuclear movement in retinal progenitor cells
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DOI：
10.1523/jneurosci.2312-05.2005
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发表时间：
2005-11-16
影响因子：
5.3
通讯作者：
Mobbs, P
中科院分区：
文献类型：
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作者：
Pearson, RA;Lüneborg, NL;Mobbs, P
在视网膜发育的早期，祖细胞必须反复分裂以扩大祖细胞池。在细胞周期的G(1)和G(2)期间，祖细胞的细胞核在称为动间运动的过程中，在增殖区来回迁移。由于分裂只能发生在脑室表面，影响核运动速度的因素可能会调节细胞周期的持续时间。缝隙连接偶联和缝隙连接依赖的Ca(2+)活性是未成熟神经系统增殖细胞的共同特征。此外，缝隙连接偶联和[Ca(2+)](I)的变化已被证明与一些未成熟细胞类型的迁移呈正相关。利用延时共聚焦显微镜，我们描述了祖细胞动间核运动的性质和速率。我们发现，核运动通常(但不总是)与Ca(2+)瞬变有关，并且用BAPTA缓冲这些瞬变会减慢运动。此外，我们首次证明缝隙连接通讯是维持视网膜前体细胞正常核运动的重要条件。传统的缝隙连接阻断剂和转染显性-负性连接蛋白43(Cx43)和Cx43特异性反义寡核苷酸(AsODN)的细胞都能减缓动间核运动。缝隙连接模拟肽Gap26也起到减慢运动的作用，我们显示的这种效果可能归因于对缝隙连接半通道的阻断。
During early retinal development, progenitor cells must divide repeatedly to expand the progenitor pool. During G(1) and G(2) of the cell cycle, progenitor cell nuclei migrate back-and- forth across the proliferative zone in a process termed interkinetic nuclear movement. Because division can only occur at the ventricular surface, factors that affect the speed of nuclear movement could modulate the duration of the cell cycle. Gap-junctional coupling and gap junction-dependent Ca(2+) activity are common features of proliferating cells in the immature nervous system. Furthermore, both gap-junctional coupling and changes in [Ca(2+)](i) have been shown to be positively correlated with the migration of a number of immature cell types. Using time-lapse confocal microscopy, we describe the nature and rate of progenitor cell interkinetic nuclear movement. We show that nuclear movement is usually, but not always, associated with Ca(2+) transients and that buffering of these transients with BAPTA slows movement. Furthermore, we show for the first time that gap-junctional communication is an important requirement for the maintenance of normal nuclear movement in retinal progenitor cells. Conventional blockers of gap junctions and transfection of cells with dominant-negative constructs of connexin 43 (Cx43) and Cx43-specific antisense oligodeoxynucleotides (asODNs) all act to slow interkinetic nuclear movement. The gap junction mimetic peptide Gap26 also acts to slow movement, an effect that we show may be attributable to the blockade of gap junction hemichannels.