R-Cadherin Is a Pax6-Regulated, Growth-Promoting Cue for Pioneer Axons
Abstract
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.
Footnotes
This work was supported by National Institutes of Health Grants NS33337 (S. S. Easter, University of Michigan, Ann Arbor, MI) and HD38069 (G.S.M.), a Nevada Agricultural Experiment Station grant (University of Nevada, Reno), and startup funds from the University of Nevada, Reno. We thank M. Takeichi for R-cadherin antibody, G. Dressler for Rcad cell lines, D. Egender, E. Hickey, and C. Corley-Mastick for cell culture advice, and N. Osumi and T. Inoue for expression plasmids and advice on whole embryo culture and electroporation.
Correspondence should be addressed to Grant Mastick, Department of Biology/200, University of Nevada, Reno, NV 89557. E-mail: ude.rnu@kcitsamg.
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