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Rejection of inappropriate synaptic partners in mouse retina mediated by transcellular FLRT2-UNC5 signaling
Developmental Cell ( IF 10.7 ) Pub Date : 2023-08-08 , DOI: 10.1016/j.devcel.2023.07.011
Cameron L Prigge 1 , Mayur Dembla 1 , Arsha Sharma 1 , Malak El-Quessny 2 , Christopher Kozlowski 1 , Caitlin E Paisley 1 , Adam M Miltner 1 , Tyler M Johnson 1 , Luca Della Santina 3 , Marla B Feller 2 , Jeremy N Kay 1
Affiliation  

During nervous system development, neurons choose synaptic partners with remarkable specificity; however, the cell-cell recognition mechanisms governing rejection of inappropriate partners remain enigmatic. Here, we show that mouse retinal neurons avoid inappropriate partners by using the FLRT2-uncoordinated-5 (UNC5) receptor-ligand system. Within the inner plexiform layer (IPL), FLRT2 is expressed by direction-selective (DS) circuit neurons, whereas UNC5C/D are expressed by non-DS neurons projecting to adjacent IPL sublayers. In vivo gain- and loss-of-function experiments demonstrate that FLRT2-UNC5 binding eliminates growing DS dendrites that have strayed from the DS circuit IPL sublayers. Abrogation of FLRT2-UNC5 binding allows mistargeted arbors to persist, elaborate, and acquire synapses from inappropriate partners. Conversely, UNC5C misexpression within DS circuit sublayers inhibits dendrite growth and drives arbors into adjacent sublayers. Mechanistically, UNC5s promote dendrite elimination by interfering with FLRT2-mediated adhesion. Based on their broad expression, FLRT-UNC5 recognition is poised to exert widespread effects upon synaptic partner choices across the nervous system.



中文翻译:


跨细胞 FLRT2-UNC5 信号介导的小鼠视网膜中不适当的突触伴侣的排斥



在神经系统发育过程中,神经元选择具有显著特异性的突触伙伴;然而,控制拒绝不适当伴侣的细胞间识别机制仍然是个谜。在这里,我们表明小鼠视网膜神经元通过使用 FLRT2-uncoordinated-5 (UNC5) 受体-配体系统来避免不合适的伴侣。在内丛状层 (IPL) 内,FLRT2 由方向选择性 (DS) 回路神经元表达,而 UNC5C/D 由投射到相邻 IPL 亚层的非 DS 神经元表达。体内 获得和功能丧失实验表明,FLRT2-UNC5 结合消除了偏离 DS 电路 IPL 亚层的生长 DS 树突。废除 FLRT2-UNC5 结合允许错误定位的乔木持续存在、精心制作并从不合适的伴侣那里获得突触。相反,DS 电路亚层中的 UNC5C 错误表达抑制树突生长并驱使乔木进入相邻的亚层。从机制上讲,UNC5 通过干扰 FLRT2 介导的粘附来促进树突消除。基于它们的广泛表达,FLRT-UNC5 识别有望对整个神经系统的突触伴侣选择产生广泛影响。

更新日期:2023-08-08
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