Eph receptors and ephrins in the developing chick cerebellum: relationship to sagittal patterning and granule cell migration.
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.
Karam
S D
SD
Department of Physiology, University of Washington, Seattle, Washington 98195, USA.
Burrows
R C
RC
Logan
C
C
Koblar
S
S
Pasquale
E B
EB
Bothwell
M
M
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology / Q000196:embryology*; D002642:Chick Embryo; D036383:Ephrin-A2; D036387:Ephrin-B1; D005326:Fetal Proteins / Q000032:analysis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D036122:Receptor, EphA4; D036183:Receptor, EphB2; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*
D036383:Ephrin-A2; D036387:Ephrin-B1; D005326:Fetal Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D020794:Receptor Protein-Tyrosine Kinases; D036122:Receptor, EphA4; D036183:Receptor, EphB2