THE PAX PROTEIN NOI IS REQUIRED FOR COMMISSURAL AXON PATHWAY FORMATION IN THE ROSTRAL FOREBRAIN

No-isthmus (Noi) is a member of the zebrafish Pax family of transcript ional regulators that is expressed in restricted domains of the develo ping CNS. In the developing eye and optic nerve, the Noi(+) cells are primitive glial cells that line the choroid fissure and optic stalk/ne rve to its junction with the optic tract, This pattern of Noi expressi on is retained in the adult, defining the optic nerve astroglia, which wrap the left and right nerves separately at the midline, thus formin g the bodily crossed optic chiasm found in fish. In embryos carrying m utations in the noi gene, the choroid fissure fails to close, glial ce lls of the optic nerve fail to differentiate and optic axons exhibit a bnormal trajectories exiting the eye and at the midline of the diencep halon. Optic axons select inappropriate pathways into the contralatera l optic nerve, rostrally towards the anterior commissure and along the ipsilateral optic tract. Noi(+) cells also border the pathway of axon s in the postoptic commissure, which is located adjacent to the optic chiasm. These postoptic commissural axons are defasciculated and also exhibit pathfinding defects in noi(-) embryos. These results indicate that Noi is required in cells that line the pathways taken by optic an d nan-optic commissural axons for guidance across the midline of the d iencephalon. We find that expression of two members of the Netrin fami ly of axon guidance molecules and the signalling protein Sonic hedgeho g is disturbed in noi(-) embryos, whereas several members of the Eph f amily of receptors and ligands show no obvious alterations in expressi on at the diencephalic midline.