Fig. 16.1.

PCP and SHH Signaling pathways. (a) Core planar cell polarity proteins asymmetrically distributed in two epithelial cells. Epithelial cells in contact with each other partition one group of proteins (FZD, DSH shown in blue) to the proximal side of the cell and another group (VANG, PK shown in orange) to the distal. FMI (shown in pink) forms a complex with FZD at the proximal surface of the membrane and VANG on the distal. Across cell junctions, FMI from one cell binds to FMI on the adjacent cell, which connects each cell within a sheet of epithelium. DSH and PK maintain asymmetry in a cell by functioning as inhibitors of each other. (b) In the absence of SHH, the pathway is in an “off” state in which PTCH (purple) inhibits SMO (green) at the cell membrane. SMO is then held captive on the membrane of vesicles (not depicted). This activates a complex of FUSED, SUFU, KIF7, and microtubules to process GLI into its transcriptional repressive form. The result is the repression of Hedgehog target genes. (c) In the “on” state, Sonic Hedgehog (pink) binds to PTCH, which relieves the repression on SMO. After SMO activation, GLI is left unprocessed and is able to enter the nucleus to stimulate Hedgehog target gene expression