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The Journal of Neuroscience, October 29, 2003, 23(30):9873-9880

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Development/Plasticity/Repair
R-Cadherin Is a Pax6-Regulated, Growth-Promoting Cue for Pioneer Axons

Gracie L. Andrews and Grant S. Mastick

Departments of Biology and Biochemistry, Cell and Molecular Biology Graduate Program, University of Nevada, Reno, Nevada 89557

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.

Key words: axon guidance; cadherin; transcription factor; pioneer axon; mutant; electroporation

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Received June 16, 2003; revised September 3, 2003; accepted September 3, 2003.

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