Normal and Abnormal Visual System
The goals of this grant are (1) to analyze the expression of retinoid metabolizing enzymes in the eye anlage; (2) to perturb normal RA levels in the eye anlage of the mouse embryo; (3) to analyze the function of aldehyde dehydrogenases; and (4) to screen for novel aldehyde dehydrogenases. During the last year we made progress towards three of these goals:
First, we succeeded in cloning the retinaldehyde dehydrogenase in the ventral embryonic retina, RALDH3. RALDH3 expression begins in the surface ectoderm over the optic recess. In rapidly changing expression patterns it labels the appearance of several ectodermal structures: it marks the formation of the lens and the olfactory organ from ectodermal placodes, and it delineates the beginning eyelid field. In addition to its expression in ocular and olfactory regions, RALDH3 synthesizes most retinoic acid in the early telencephalon. It is expressed at high levels in the ganglionic eminence, a large germinal zone of the embryonic forebrain.
The second completed project is an extensive molecular, morphological and functional analysis of the role of retinoic acid in the formation of the dorso-ventral retina and its central projections. We described how dynamic expression patterns of four retinoid metabolizing enzymes create rapidly changing retinoic acid (RA) patterns in the emerging eye anlage of the mouse. First, a RA-rich ventral zone is set up, then a RA-poor dorsal zone, and finally a tripartite organization consisting of dorsal and ventral RA-rich zones separated by a horizontal RA-poor stripe. This subdivision of the retina into three RA concentration zones is directly visible as b-galactosidase labeling patterns in retinas of RA reporter mice. Because the axons of retinal ganglion cells transport the reporter product anterogradely, the central projections from dorsal and ventral retina can be visualized as two heavily labeled axon bundles. Comparisons of the axonal labeling with physiologic recordings of visual topography in the adult mouse show that the labeled axons represent the upper and the lower visual fields. The RA-poor stripe develops into a broad horizontal zone of higher visual acuity. Comparisons of the retina labeling with eye-muscle insertions show that the axis of the RA pattern lines up with the dorso-ventral axis of the oculomotor system. These observations indicate that the dorso-ventral axis of the embryonic eye anlage determines the functional coordinates of both vision and eye movements in the adult.