The genetic basis of patterned baldness in Drosophila

Abstract

Norbert Perrimon Howard Hughes Medical Institute Department of Genetics Harvard Medical School Boston, Massachusetts 02115 Studies of segment polarity genes, which specify cellular identities within the Drosophila segmented embryonic epi- dermis, have identified two secreted proteins, wingless (wg) and hedgehog (hh), that play key roles in instructing cells about their fates within the segments. These mole- cules appear to function as signals in two temporally dis- tinct pathways. First, through short-range interactions, cells expressing the wg and hh signals stabilize their mu- tual expression. Second, these signals pattern cell types at a distance, acting either as morphogens or by the trig- gering of a cascade of local signaling responses and ulti- mately a determination of whether epidermal cells differ- entiate various kinds of hairs or naked cuticle. The functions of many other segment polarity genes can be explained either as regulators or transducers within the signaling pathways of these two primary signals. Wg and hh are also implicated in long-range signaling that estab- lishes cellular patterning within the imaginal discs. The components that mediate the wg and hh effects in both the embryo and imaginal discs are similar, indicating that these signals activate biochemical cascades that have been conserved between cell types. Identification of these molecules in vertebrates also suggests that these path- ways have been conserved during evolution. lntrasegmental patterning In the Drosophila embryo, the first morphological sign of segmentation begins at mid-stage 10 with the formation of metameric units or parasegments (Figure 1). The anterior boundaries of the pair rule genes fus/?Ctafazu and even-