Fig. 7.

Proposed coloboma mechanism in Lrp6-null eyes and a possible signaling network during early eye development. A: Genetic deletion of Lrp6 severely reduces expression of the dorsal retina marker genes and leads to substantial reduction or elimination of the dorsal retina territory in Lrp6-null embryos, resulting in dorsal expansion/shift of ventral neural retina territory. The dorsal shifting of the ventral retina may lead to coloboma in the ventral eye region. Arrowhead indicates the closure site of the optic cup/optic fissure at embryonic day (E) 10.5. B: We propose a possible molecular mechanism or a signaling network for early eye development that Lrp6 (and its mediated canonical Wnt signaling pathway) is acting upstream of the Bmp4 and RA signaling pathways in the dorsal eye region and plays significant roles in establishing dorsoventral retina boundaries and related morphogenetic movements. The known roles of Bmp4 and retinoic acid (RA) signaling pathways for early eye development are summarized from the literature. Dashed arrows indicate direct or indirect regulations. Solid arrows indicate the direct regulations.