Eph receptors and ephrins in the developing chick cerebellum: Relationshipto sagittal patterning and granule cell migration

Spatiotemporal expression patterns of six members of the Eph gene family (E phA4, EphA3, EphB2, ephrin-B1, ephrin-A2, and ephrin-A5) were characterized immunocytochemically at various stages of chick cerebellar development. Ep hA4 expression is observed in the cerebellar anlage as early as embryonic d ay 5 (E5) and continues in the posthatch cerebellum. During the early perio d of cerebellar development (E3-E8), complementarity is observed between Ep hA4 and ephrin-A5 expression within the cerebellar-isthmal region. By E8, d ifferential expression of EphA4 in parasagittal Purkinje cell bands is evid ent, and the expression remains banded in the posthatch cerebellum. Banded expression of the ephrin-A5 ligand complements EphA4 expression during the middle period (E9-E15). During this period, ephrin-A2 and EphA3 are coexpre ssed in a banded pattern and with variable correlation to EphA4. Variabilit y in the banding expression is observed for EphA4, EphA3, ephrin-A5, and ep hrin-A2 across different lobes, and graded complementarity in the expressio n pattern of EphA3 and ephrin-A5 is observed in the external granular layer between the posterior and anterior lobes. Analysis of Purkinje cell birth date in correlation with Eph-ephrin expression during the middle period rev eals that early-born cells express EphA4, whereas late-born cells express e phrin-A5. Finally, EphA4 expression domains are respected by migrating gran ule cell ribbons, which express both ephrin-B1 and EphB2. These expression patterns suggest multiple roles for the Eph-ephrin system in cerebellar dev elopment, including demarcation/enforcement of boundaries of the cerebellar anlage, formation/maintenance of Purkinje cell compartments, and restricti on of the early phase of granule cell migration to ribbons.