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The Journal of Neuroscience, September 1, 2000, 20(17):6488-6500

Eph Receptors and Ephrins in the Developing Chick Cerebellum: Relationship to Sagittal Patterning and Granule Cell Migration

Sana D. Karam¹, Robert C. Burrows², Cairine Logan³, Simon Koblar⁴, Elena B. Pasquale⁵, and Mark Bothwell¹

Departments of ¹ Physiology and Biophysics and ² Radiology, University of Washington, Seattle, Washington 98195, ³ Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, T2N 4N1, Canada, ⁴ Department of Genetics, University of Adelaide, Adelaide, South Australia, 5005, Australia, and ⁵ The Burnham Institute, La Jolla, California 92037

Spatiotemporal expression patterns of six members of the Eph gene family (EphA4, EphA3, EphB2, ephrin-B1, ephrin-A2, and ephrin-A5) were characterized immunocytochemically at various stages of chick cerebellar development. EphA4 expression is observed in the cerebellar anlage as early as embryonic day 5 (E5) and continues in the posthatch cerebellum. During the early period of cerebellar development (E3-E8), complementarity is observed between EphA4 and ephrin-A5 expression within the cerebellar-isthmal region. By E8, differential expression of EphA4 in parasagittal Purkinje cell bands is evident, 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 coexpressed in a banded pattern and with variable correlation to EphA4. Variability in the banding expression is observed for EphA4, EphA3, ephrin-A5, and ephrin-A2 across different lobes, and graded complementarity in the expression 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 reveals that early-born cells express EphA4, whereas late-born cells express ephrin-A5. Finally, EphA4 expression domains are respected by migrating granule cell ribbons, which express both ephrin-B1 and EphB2. These expression patterns suggest multiple roles for the Eph-ephrin system in cerebellar development, including demarcation/enforcement of boundaries of the cerebellar anlage, formation/maintenance of Purkinje cell compartments, and restriction of the early phase of granule cell migration to ribbons.

Key words: Purkinje cell; Eph; ephrin; compartmentation; stripes; bands; BrdU; birth dating; chick; cerebellum; granule cell; raphes; ribbons; migration; development

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20176488-13$05.00/0

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