The L1-type adhesion molecule Neuroglian controls glial development and optic lobe morphogenesis in Drosophila

Glial development is essential for establishing the architecture and connectivity of the Drosophila visual system. However, the molecular programs that coordinate glial proliferation, differentiation, migration and wrapping during optic lobe maturation remain incompletely defined. Here, we identify the homophilic L1-type adhesion molecule Neuroglian (Nrg) as a key regulator of glial development and tissue-scale remodeling in the developing optic lobe. Glia-specific depletion of Nrg disrupts the characteristic lamina-medulla rotation during pupation, causes fragmentation and loss of continuity of wrapping-glial membranes, and significantly reduces the number of glial cells, accompanied by increased glial apoptosis and only marginal changes in glial proliferation after normalization to total glial cell number, revealing a broad requirement for Nrg across multiple stages of glial development. Subtype-specific knockdown demonstrates that giant chiasm glia and cortex glia are important for Nrg-mediated glial development, migration and differentiation as well as axon wrapping and proper optic lobe geometry. Finally, using isoform-specific endogenous tagging, we show that Nrg167, rather than Nrg180, is the predominant glial isoform from the third-instar larval stage through adulthood. Together, our findings establish an isoform-specific, glia-intrinsic role for Nrg in coupling cellular morphogenesis to organ-level visual system assembly and highlight cell adhesion molecules as a core determinant of neural tissue architecture.