Retinal ganglion cell migration and viability requires the kinase LKB1.

Abstract

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.