Six6 (Optx2) is a novel murine Six3-related homeobox gene that demarcates the presumptive pituitary/hypothalamic axis and the ventral optic stalk

We report on the isolation of a murine homeobox-containing gene, Six6 (Optx 2), that shows extended identity in its coding region with Six3, the only m ember of the mammalian Six gene family known to be expressed in the optic p rimordium. Phylogenetic analysis demonstrates that Six6 and Six3 belong to a separate group of homeobox-genes that art: closely related to the recentl y identified Drosophila optix. Earliest Six6 expression was detected in the Boor of the diencephalic portion of the primitive forebrain, a region pred icted to give rise to the neurohypophysis and to the hypothalamus. Later on , Six6 mRNA was found in the primordial tissues giving rise to the mature p ituitary: the Rathke's pouch and the infundibular recess. In the optic prim ordium, Six6 demarcates the presumptive ventral optic stalk and the ventral portion of the future neural retina. In the developing eye, Six6 expressio n was detected in the neural retina, the optic chiasma and optic stalk, but nut in the lens. When compared to Six6, Sid expression pattern was highly similar, but with a generally broader transcripts distribution in the brain and in the visual system. We finally show that Six6 does not require Pax6 for its expression in the optic primordium, suggesting that Six6 acts on a parallel and/or independent pathway with Pax6 in the genetic cascade govern ing early development of the eye. (C) 1999 Elsevier Science Ireland Ltd. Al l rights reserved.