Mackin Robert D, Bhalla Ritika V, Akhanov Viktor, Abdulwahab Qudrat T, Burger Courtney A, Samuel Melanie A
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital , Houston, TX, USA.
J Cell Biol. 2025 Jul 7;224(7). doi: 10.1083/jcb.202410023. Epub 2025 Jun 11.
The arrangement of neurons into ordered layers underlies circuit function in many nervous system regions. This is particularly true in the mammalian retina. Here, fate-committed retinal ganglion cells (RGCs) migrate from the apical to the inner retina, where they form connections that enable vision. The mechanisms that permit ganglion cell migration and whether distinct ganglion cell types use different migration modes are unknown. We show that the serine/threonine kinase LKB1 regulates ganglion cell migration and nuclear positioning. In the absence of LKB1, many ganglion cells remain in the apical retina. Misplaced cells show modified morphologies and display altered cytoskeletal proteins. Examination of RGC types revealed that LKB1 is specifically required to promote F-type RGC (F-RGC) migration. The failure of F-RGCs to migrate results in a significant F-RGC loss via increased cell death and microglia engulfment. Together, these results identify molecular determinates of ganglion cell migration and indicate that different ganglion cell types can use distinct programs to ensure their localization.
神经元排列成有序的层次是许多神经系统区域回路功能的基础。在哺乳动物视网膜中尤其如此。在这里，命运已确定的视网膜神经节细胞（RGCs）从视网膜顶端迁移到视网膜内层，在那里它们形成使视觉成为可能的连接。允许神经节细胞迁移的机制以及不同类型的神经节细胞是否使用不同的迁移模式尚不清楚。我们发现丝氨酸/苏氨酸激酶LKB1调节神经节细胞的迁移和细胞核定位。在没有LKB1的情况下，许多神经节细胞仍留在视网膜顶端。位置错误的细胞表现出形态改变，并显示细胞骨架蛋白发生变化。对RGC类型的检查表明，LKB1是促进F型RGC（F-RGC）迁移所特别需要的。F-RGC迁移失败会导致通过细胞死亡增加和小胶质细胞吞噬而使F-RGC显著减少。总之，这些结果确定了神经节细胞迁移的分子决定因素，并表明不同类型的神经节细胞可以使用不同的程序来确保它们的定位。
