A potential role for the OTX2 homeoprotein in creating early 'highways' for axon extension in the rostral brain

Brain pattern formation starts with a subdivision of the neuroepithelium th rough site-specific expression of regulatory genes and, subsequently, the b oundaries between presumptive neuromeres may provide a scaffold for early f ormation of axon tracts. fn the mouse forebrain, the transcription factor O TX2 is strongly expressed at several such boundaries. Combining dye tracing and staining for OTX2 protein, we show that a number of early fibre tracts develop within stripes of OTX2 expression. To analyse a putative influence of OTX2 on the expression of molecules involved in neurite growth, we gene rated several clones of NIH3T3 cells stably expressing OTX2 protein at vary ing levels, As shown by immunoblotting, Otx2 transfection affects the expre ssion of a variety of cell and substratum adhesion molecules, rendering the cells a favourable substratum in neurite outgrowth assays. Among the molec ules upregulated with increasing levels of OTX2 are NCAM, tenascin-C and DS D-1-PG, which also in situ colocalize with zones of OTX2 expression at boun daries. These data suggest that Otx2 might be involved in defining local su bstrata for axon extension in the forebrain.