Figure 4. Canonical Wnt/b-catenin signaling during development of the anterior segment.

(A) (Left) Both the LRP5/6 and Fz proteins are present on the surface of a competent cell, providing available Wnt ligand with the full heterodimeric receptor required to transduce the signal. Activation of the full receptor by Wnt ligand induces biochemical changes within the cytoplasm that lead to accumulation of stabilized β-catenin, which is translocated to the nucleus where it activates transcription of target genes. (Right) DKK proteins, when present, render a cell incompetent to respond to Wnt ligand because the LRP5/6 component required for receptor function is removed from the cell membrane. DKK proteins bind LRP5/6, in combination with a third protein called Kremen, and this complex is cleared from the cell surface by endocytosis and subsequently degraded. This leaves the cell incompetent to transduce a signal to the nucleus, even when high quantities of Wnt ligand present, because a fully functional heterodimeric receptor cannot be formed. (B) Summary of Wnt ligand and Frizzled receptor expression sites (blue) in mouse eye tissues at e12.5. (C) Summary of structures/cells exhibiting high (blue) or low (white) canonical Wnt signaling activity in mouse eye tissues at e12.5. Key: BC, bulbar conjunctiva; C, cornea; L, lens; Dkk, Dickkopf; Fz, any frizzled protein; Krm, Kremen; LRP5/6, low density lipoprotein receptor-related protein 5 or 6; M, mesenchyme; PC, palpebral conjunctiva; PE, palpebral epidermis; TCF, transcription factor 4; Wnt, Wnt ligand