Multiple Roles of Ephrins during the Formation of Thalamocortical Projections: Maps and More

Jürgen Bolz, Daniela Uziel, Sven Mühlfriedel, André Güllmar, Christiane Peuckert, Konstantinos Zarbalis, Wolfgang Wurst, Masaaki Torii, Pat Levitt

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


The functional architecture of the cerebral cortex is based on intrinsic connections that precisely link neurons from distinct cortical laminae as well as layer-specific afferent and efferent projections. Experimental strategies using in vitro assays originally developed by Friedrich Bonhoeffer have suggested that positional cues confined to individual layers regulate the assembly of local cortical circuits and the formation of thalamocortical projections. One of these wiring molecules is ephrinA5, a ligand for Eph receptor tyrosine kinases. EphrinA5 and Eph receptors exhibit highly dynamic expression patterns in distinct regions of the cortex and thalamus during early and late stages of thalamocortical and cortical circuit formation. In vitro assays suggest that ephrinA5 is a multifunctional wiring molecule for different populations of cortical and thalamic axons. Additionally, the expression patterns of ephrinA5 during cortical development are consistent with this molecule regulating, in alternative ways, specific components of thalamic and cortical connectivity. To test this directly, the organization of thalamocortical projections was examined in mice lacking ephrinA5 gene expression. The anatomical studies in ephrinA5 knockout animals revealed a miswiring of limbic thalamic projections and changes in neocortical circuits that were predicted from the expression pattern and the in vitro analysis of ephrinA5 function.

Original languageEnglish (US)
Pages (from-to)82-94
Number of pages13
JournalJournal of Neurobiology
Issue number1
StatePublished - Apr 2004
Externally publishedYes


  • Axonal guidance
  • Cortical development
  • Ephrin
  • Wiring molecules

ASJC Scopus subject areas

  • Neuroscience(all)


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