The result is a large area of proximally pointing hairs in this region. This reversal of polarity is seen when fz expression is induced just before the start of hair morphogenesis, at the time polarity is established, suggesting that the gradient of Fz protein acts fairly directly to reverse hair polarity. The finding that functional dsh is required for the reversal of polarity argues that the reversal requires normal fz signal transduction. The data suggest that cells sense the level of Fz protein on neighboring cells and use this information in order to polarize themselves. A polarizing signal is transmitted from cells with higher Fz levels to cells with lower levels.
Recent evidence points to a role for lipid signaling downstream of Frizzled proteins.
The release of intracellular calcium is suppressed by an inhibitor of the enzyme inositol monophosphatase, and hence of the phosphatidylinositol signaling pathway. This suppression can be rescued by injection of the compound myo-inositol, which overcomes the decrease in this intermediate caused by the inhibitor. Since Gbetagamma subunits also activate protein kinase C, which may be involved in Wnt signaling, the responses by cells and embryos to signaling through Frizzled homologs could involve the stimulation of multiple cytoplasmic pathways. Fz2 has a higher affinity for Wg than Fz, and removal of either Fz or Fz2 has subtle, but different, effects on the patterning of the embryonic nervous system. Overexpression of Fz2 in the developing wing activates Wg-Arm targets.