Abstract
Neural maps in the vertebrate central nervous system often show discontinuously segregated, domain-to-domain patterns. However, the molecular mechanism that establishes such maps is not well understood. Here we show that in the chicken olivocerebellar system, EphA receptors and ephrin-As are expressed with distinct levels and combinations in mapping domains. When ephrin-A2 is retrovirally overexpressed in the cerebellum, the olivocerebellar map is disrupted, excluding axons with high receptor activity from ectopic expression domains. Conversely, overexpression of a truncated EphA3 receptor in the cerebellum reduces endogenous ligand activity to undetectable levels and causes aberrant mapping, with high receptor axons invading high ligand domains. In vitro, ephrin-A2 inhibits outgrowth of inferior olive axons in a region-specific manner. These results suggest that Eph receptors and ephrins constitute domain-specific positional information, and the spatially accurate receptor-ligand interaction is essential to guide inferior olive axons to their correct target domains.
Original language | English |
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Pages (from-to) | 5647-5658 |
Number of pages | 12 |
Journal | Development |
Volume | 129 |
Issue number | 24 |
DOIs | |
Publication status | Published - 15 Dec 2002 |
Keywords
- Eph receptors
- ephrins
- olivocerebellar projection
- CNS
- developing chick cerebellum
- retinal axon guidance
- ganglion-cell axons
- tyrosine kinase
- visual-system
- lateral position
- purkinje-cells
- ROBO receptors
- in-vitro
- expression