OCULAR AND CEREBELLAR DEFECTS IN ZEBRAFISH INDUCED BY OVEREXPRESSION OF THE LIM DOMAINS OF THE ISLET-3 LIM HOMEODOMAIN PROTEIN/

Islet-3 is an LIM/homeodomain protein that is expressed specifically i n the eyes and the presumptive tectum in the central nervous system of zebrafish (Danio rerio) embryos. Overexpression of the protein (LIM(I sl-3))consisting only of the Islet-3 LIM domains in embryos specifical ly prevented formation of the optic vesicles; caused abnormal terminat ion of the expression of wnt1, engrailed2, and pax2 in the mesencephal ic and metencephalic region between 14 hr and 20 hr postfertilization; and severely impaired morphogenetic movement in this region between 2 0 hr and 26 hr, which should normally lead to formation of the cerebel lar primordium. Such defects were all rescued by simultaneous overexpr ession of Islet-3, suggesting that LIM(Isl-3) acted as a specific domi nant-negative variant of Islet-3. These data, combined with the result s of mosaic analyses, suggest that Islet-3 is activated by putative LI M-binding cofactors and functions to promote evagination of the optic vesicles and to maintain reciprocal interaction between the mesencepha lon and the mesencephalic-metencephalic boundary essential for normal development of this region.