Critical roles for EphB and ephrin-B bidirectional signalling in retinocollicular mapping
Critical roles for EphB and ephrin-B bidirectional signalling in retinocollicular mapping
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DOI：
10.1038/ncomms1445
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发表时间：
2011-08-01
影响因子：
16.6
通讯作者：
Henkemeyer, Mark
中科院分区：
文献类型：
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作者：
Thakar, Sonal;Chenaux, George;Henkemeyer, Mark
EphB和Ephin-B沿视网膜背腹轴的分级表达表明，这些双向信号分子在背腹侧-内侧视网膜绒毛定位中发挥了作用。尽管以前的研究表明EphB2在小鼠中起正向信号作用，但EphB2在视网膜小球定位中所必需的细胞内成分以及EphB1、ePhin-B1和ePhin-B2的作用尚不清楚。在这里，我们表明，EphB2酪氨酸激酶催化活性和EphB1细胞内信号是腹侧-颞侧视网膜神经节细胞轴突视网膜小球定位的关键中介，可能通过与上丘中的ePhin-B1相互作用。我们进一步阐明了ewitin-B2细胞内结构域在视网膜小球定位中的作用，并提出了意想不到的发现，即背侧和腹侧视网膜神经节细胞轴突都利用反向信号进行地形图定位。这些数据表明，EphB和Ephin-B相互作用所启动的正向和反向信号在上丘内外侧轴的视网膜背腹侧神经节细胞轴突终止中起主要作用。
Graded expression of EphB and ephrin-B along the dorsoventral axis of the retina indicates a role for these bidirectional signalling molecules in dorsoventral-mediolateral retinocollicular mapping. Although previous studies have implicated EphB2 forward signalling in mice, the intracellular component of EphB2 essential for retinocollicular mapping is unknown as are the roles for EphB1, ephrin-B1, and ephrin-B2. Here we show that EphB2 tyrosine kinase catalytic activity and EphB1 intracellular signalling are key mediators of ventral-temporal retinal ganglion cell axon retinocollicular mapping, by likely interacting with ephrin-B1 in the superior colliculus. We further elucidate roles for the ephrin-B2 intracellular domain in retinocollicular mapping and present the unexpected finding that both dorsal and ventral-temporal retinal ganglion cell axons utilize reverse signalling for topographic mapping. These data demonstrate that both forward and reverse signalling initiated by EphB: ephrin-B interactions have a major role in dorsoventral retinal ganglion cell axon termination along the mediolateral axis of the superior colliculus.