Medaka eyeless is the key factor linking retinal determination and eye growth

The complete absence of eyes in the medaka fish mutation eyeless is the res ult of defective optic vesicle evagination. We show that the eyeless mutati on is caused by an intronic insertion in the Rx3 homeobox gene resulting in a transcriptional repression of the locus that is rescued by injection of plasmid DNA containing the wild-type locus. Functional analysis reveals tha t Six3- and Pax6- dependent retina determination does not require Rx3. Howe ver, gain- and loss-of-function phenotypes show that Rx3 is indispensable t o initiate optic vesicle evagination and to control vesicle proliferation, by that regulating organ size. Thus, Rx3 acts at a key position coupling th e determination with subsequent morphogenesis and differentiation of the de veloping eye.