R-Cadherin Is a Pax6-Regulated, Growth-Promoting Cue for Pioneer Axons

The transcription factor Pax6 has been implicated in two processes that may be related in brain development: establishment of regional cell adhesion properties and axon guidance. In Pax6 mutant mouse embryos, forebrain pioneer axons make pathfinding errors. These errors occur in a region of the ventral thalamus in which the expression of the cell adhesion molecule R-cadherin (Cdh4) is lost in Pax6 mutants. In vitro, an R-cadherin substrate promoted pioneer axon outgrowth. Furthermore, pioneer axon outgrowth was rescued in vivo by selective replacement of R-cadherin by electroporation into cultured Pax6 mutant embryos. Thus, these studies implicate Pax6 as an early brain patterning gene that establishes regional adhesive codes to guide pioneer axons.