We first examined the transcriptional patterns of Fat1 and Fat4 during eye development (
Fig. 1). No distinct expression of either
Fat gene was detected in the lens placode or optic cup at E9.5 (
Figs. 1A,
1B). The first signal for Fat4 was detected in lens pit cells at E10.5 (
Fig. 1D, arrow) while Fat1 was not detected at this stage (
Fig. 1C). The lens vesicle has formed by E11.5 and a transient signal in the posterior cells of the vesicle was detected with Fat1 probes (
Fig. 1E, arrow) but the expression of Fat4 was confined to the anterior cells of the vesicle (
Fig. 1F, arrow). By E12.5, cells in the posterior part of the vesicle have begun to elongate into primary fibers and both Fat1 and Fat4 were excluded from the primary fibers but localized to the anterior cells of the vesicle that differentiate into the lens epithelium (
Figs. 1G, 1H). From this stage on, little or no Fat1 or Fat4 expression was detected in the lens fibers and prominent expression was restricted to the lens epithelial cells (
Figs. 1I–L). Fat1/4 expression was also detected to varying degrees in mesenchymal cells in the vicinity of the developing eye (
Figs. 1E–H, asterisks). Expression of both
Fat genes was similarly detected in the optic cup at E12.5 (
Figs. 1G, 1H, arrowheads). At later stages the expression of both Fat1 and Fat4 was detected at the distal margin of the optic cup that forms the ciliary body and iris (
Figs. 1I–L, large arrowheads). In neural retina Fat1 was detected in the outer layers (
Figs. 1I, 1K', small arrowheads), while Fat4 expression was detected in the inner layers (
Fig. 1J, small arrowheads). By E18.5 Fat4 expression formed a distinct lamina in the inner layer (
Fig. 1L', arrowheads).