Abstract
Background: The frizzled (fz) gene of Drosophila is the founding member of
the large family of Wnt receptors. This gene was originally studied for its role
in the generation of tissue polarity in the adult epidermis, where it is at the
center of an intercellular signaling and intracellular signal transduction
pathway. Mutations in members of the fz signaling/signal transduction pathway
disrupt tissue polarity. On the wing, this results in altered polarity of the
hairs that cover the wing, which normally point distally.
Results: We devised a novel method to locally induce the expression of a fz
transgene under the control of the hsp70 promoter. Application of a drop of hot
wax at the distal end of the pupal wing induced a gradient of frizzled
expression with a high point near the distal tip. This resulted in a large area
of proximally pointing hairs in this region. This remarkable reversal of normal
hair polarity was seen when the gradient of expression was induced just prior to
the start of hair morphogenesis when hair polarity is set, suggesting that the
gradient of Fz protein acted in a fairly direct way to reverse hair polarity. A
similar induction of the dishevelled gene, which acts in a cell autonomous
fashion and functions downstream of frizzled in tissue polarity, resulted in a
tissue polarity phenotype, but no region of reversed polarity. This argues that
the cell nonautonomous function of fz was essential for production of a region
of reversed polarity. Furthermore, the finding that a functional dishevelled
gene was required for the effect argues that the normal fz signal transduction
pathway was used when hair polarity was reversed.
Conclusions: The data
suggest that cells can sense the level of Frizzled protein on neighboring cells
and that this information can be used to polarize cells. The data indicate that
tissue polarity points from cells of higher to cells of lower Fz levels. This
provides new ways to explain aspects of tissue polarity and provides a potential
general mechanism to explain how Wnts can polarize target cells.