Fig. 8. Model for Slit-mediated glial bridge and commissure formation in wild-type and Hh mutant zebrafish embryos. (A) slit2 and slit3 (blue) are normally expressed posterior to the POC and in bands adjacent to the AC. We propose that Slit2 and Slit3 repulsion creates corridors that prevent Robo-expressing glial and axonal cell migration into slit2/slit3-expressing domains. By contrast, slit1a expression (yellow) in the preoptic area and dorsal telencephalon overlaps with the forebrain glial bridges and forebrain commissures, suggesting either that (1) Slit1a provides a permissive or attractant cue for these cells, or (2) that Slit1a is less repellent for glia and commissural axons than Slit2/Slit3, causing glial cells and commissural axons to position themselves on slit1a-expressing cells just anterior to the slit2/slit3 expression domain. Slit expression in the telencephalon also suggests a role in AC formation. Gfap+ cells (red) may provide a positive or permissive substrate for AC, POC and RGC axon (green) growth across the midline. (B) In yot (gli2DR) mutants, RGC axons and POC axons fail to cross the midline. In addition, Gfap+ cells are reduced in the POC/chiasm region and spread into the pre-optic area. slit2/slit3 expression is expanded across the commissure regions, whereas slit1a expression is reduced. slit MO injections show that expansion of slit2/slit3 expression is the major cause of midline crossing errors in yot (gli2DR) mutants (black bars). (C) Schematic lateral view of Robo expression in the POC/chiasm region. RGC axons express robo2 (Lee et al., 2001), POC neurons express robo1, robo2 and robo3 (green), all Gfap+ cells express robo1 and robo3 (red and orange), but anterior Gfap+ cells also express robo4 (orange). (D,E) Illustration of shh expression (purple) in relation to axons and glial cells in the forebrain at 30 hpf from frontal (D) and lateral (E) views. Shh leads to the repression of slit2/slit3 expression but positively regulates slit1a expression (dashed arrows). Currently, it is unknown whether Shh regulates Slit expression in the AC region (?).