Eph receptors and ephrins demarcate cerebellar lobules before and during their formation

The formation of the ten cerebellar lobules is an unsolved problem in brain development. We report a screen for the four subfamilies of Eph receptors and their ligands (ephrins) in developing mouse cerebellum, using soluble r eceptor-immunoglobulin and ligand-immunoglobulin fusion proteins, and antib odies against EphA and ephrin-B proteins. Our results identify Eph receptor s and ephrins as the first molecules known to demarcate individual lobules during development. Staining for ephrin-A ligands is in lobule Vm as it for ms, across the whole width of the cerebellum. Staining for three EphA recep tors approximately coincides with presumptive lobules VI and/or VII before and just after birth, whereas a fourth EphA receptor (EphA4, which binds li gands of both subfamilies) has more widespread expression. Staining for Eph B receptors is in lobules VII, Vm, and IX. Staining for ephrin-B ligands is much weaker, becomes detectable only after birth, and does not appear to b e lobule-specific. Staining for all subfamilies spreads to at least some ad jacent lobules as maturation proceeds. The lobule-specific patterns appear before the lobules form, and initially extend across the width of the cereb ellum, in spite of the lesser conservation of the lateral extensions of the lobules. These expression patterns define previously unknown developmental units and suggest that Eph family proteins may contribute to cerebellar mo rphogenesis. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.