Distinct timing of neurogenesis of ipsilateral and contralateral retinal ganglion cells.

Distinct timing of neurogenesis of ipsilateral and contralateral retinal ganglion cells.
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DOI:
10.1002/cne.24467
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发表时间:
2019-01-01
期刊:
The Journal of comparative neurology
影响因子:
--
通讯作者:
Mason C
Mason C
中科院分区:
其他
文献类型:
--
作者:
Marcucci F;Soares CA;Mason C

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在高等脊椎动物中,视网膜神经节细胞(RGC)投射到大脑的同侧(IRGC)或对侧(CRGCs)形成的回路允许双目视觉和深度感知。IRGCs和cRGCs在视网膜中的位置不同,在转录、导向和活性相关因子的表达上也不同。为了分析这两个群体在出生时间上是否也不同,这是不同神经亚型和相关投射的特征,我们使用了新的出生方法和细胞亚型特定标记来比以前更准确地确定出生日期和细胞周期退出。在腹颞(VT)视网膜,I-和cRGC混合,该区域的神经发生滞后于RGC的产生,而在视网膜的其余部分,只有cRGC位于那里。此外,在VT视网膜内,i-和cRGC群体在不同的时间出生:iRGC的神经发生在E13出现高峰,cRGCs最早在E14出现,而不是像报道的那样在胚胎发育中较晚。此外,在腹侧纤毛缘区(CMZ)中,含有在腹侧神经视网膜中产生一些iRGC的前体细胞,细胞周期退出比在其他视网膜区域慢,在其他区域,前体细胞只产生cRGC。此外,当细胞周期调节因子Cyclin D2缺失时,CMZ中的细胞周期长度进一步缩短,反映了Cyclin D2突变体中I-和cRGC的减少。这些结果强化了在祖细胞水平上细胞周期动力学的差异调节与特定的RGC命运和轴突投射的偏侧性相关的观点。通过特定的标志物和出生测定方法(EDU),我们绘制了IPSI和对侧RGC的神经发生图。IPSI RGC的神经发生落后于视网膜其他部位的对侧RGC,但与腹侧视网膜的对侧RGC相似。细胞周期蛋白D2在VT视网膜产生RGCs过程中起重要作用。
In higher vertebrates, the circuit formed by retinal ganglion cells (RGCs) projecting ipsilaterally (iRGCs) or contralaterally (cRGCs) to the brain permits binocular vision and depth perception. iRGCs and cRGCs differ in their position within the retina and in expression of transcription, guidance and activity-related factors. To parse whether these two populations also differ in the timing of their genesis, a feature of distinct neural subtypes and associated projections, we used newer birthdating methods and cell subtype specific markers to determine birthdate and cell cycle exit more precisely than previously. In the ventrotemporal (VT) retina, i- and cRGCs intermingle and neurogenesis in this zone lags behind RGC production in the rest of the retina where only cRGCs are positioned. In addition, within the VT retina, i- and cRGC populations are born at distinct times: neurogenesis of iRGCs surges at E13, and cRGCs arise as early as E14, not later in embryogenesis as reported. Moreover, in the ventral ciliary margin zone (CMZ), which contains progenitors that give rise to some iRGCs in ventral neural retina, cell cycle exit is slower than in other retinal regions in which progenitors give rise only to cRGCs. Further, when the cell cycle regulator Cyclin D2 is missing, cell cycle length in the CMZ is further reduced, mirroring the reduction of both i- and cRGCs in the Cyclin D2 mutant. These results strengthen the view that differential regulation of cell cycle dynamics at the progenitor level is associated with specific RGC fates and laterality of axonal projection. With specific markers and birthdating methods (EdU), we charted the neurogenesis of ipsi- and contralateral RGCs. Ipsi RGC neurogenesis lags behind that of contra RGCs elsewhere in the retina, but is similar to contra RGCs in ventrotemporal retina. Cyclin D2 is important for the production of RGCs from VT retina.
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