Developmental regulation of long-range neuroblast migration by Eph/ephrin signaling

In the developing mouse anterior forebrain, the rostral migratory stream (RMS) supports continued proliferation and efficient transportation of large quantities of neuroblasts from the ventricular-subventricular (V-SVZ) stem cell niche to the olfactory bulb (OB). Astrocytes aid this migration by providing a glial network through which chains of fasciculated neuroblasts move. The largest receptor tyrosine kinase family, Eph receptors, and their ephrin ligands have been implicated in controlling neuroblast migration and astrocyte organization within this pathway. However, a clear understanding of the regulatory mechanisms underlying Eph/ephrin signaling remains elusive, in part due to the complexity of heterogeneous expression patterns in both neuroblasts and astrocytes, as well as the cytoarchitectural changes that occur during postnatal development. Our studies provide a framework to deconvolute and characterize Eph and ephrin signaling as the RMS changes from a diffuse stream of migratory neuroblasts to a highly constricted pathway of neuroblast chains within astrocytic networks. Specifically, we identify temporally regulated, cell type-specific receptor-ligand interactions, revealing the prevalence and dynamic shifts of neuroblast-neuroblast, neuroblast-astrocyte, astrocyte-astrocyte interactions. Mice were harvested at P6, P12, or P60 ages. Their brains were harvested, and the rostral migratory stream was microdissected. Live cells were sorted by FACS from dead cells and debris and analyzed using scRNA seq.