Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing.

The Drosophila wing is formed by two cell populations, the anterior and posterior compartments, which are distinguished by the activity of the selector gene engrailed (en) in posterior cells. Here, we show that en governs growth and patterning in both compartments by controlling the expression of the secreted proteins hedgehog (hh) and decapentaplegic (dpp) as well as the response of cells to these signaling molecules. First, we demonstrate that en activity programs wing cells to express hh whereas the absence of en activity programs them to respond to hh by expressing dpp. As a consequence, posterior cells secrete hh and induce a stripe of neighboring anterior cells across the compartment boundary to secrete dpp. Second, we demonstrate that dpp can exert a long-range organizing influence on surrounding wing tissue, specifying anterior or posterior pattern depending on the compartmental provenance, and hence the state of en activity, of the responding cells. Thus, dpp secreted by anterior cells along the compartment boundary has the capacity to organize the development of both compartments. Finally, we report evidence suggesting that dpp may exert its organizing influence by acting as a gradient morphogen in contrast to hh which appears to act principally as a short range inducer of dpp

A Feed-Forward Circuit Linking Wingless, Fat-Dachsous Signaling, and the Warts-Hippo Pathway to Drosophila Wing Growth

The secreted morphogen Wingless promotes Drosophila wing growth by fueling a wave front of Fat-Dachsous signaling that recruits new cells into the wing primordium

Mutations in the Polycomb Group Gene polyhomeotic Lead to Epithelial Instability in both the Ovary and Wing Imaginal Disc in Drosophila

Most human cancers originate from epithelial tissues and cell polarity and adhesion defects can lead to metastasis. The Polycomb-Group of chromatin factors were first characterized in Drosophila as repressors of homeotic genes during development, while studies in mammals indicate a conserved role in body plan organization, as well as an implication in other processes such as stem cell maintenance, cell proliferation, and tumorigenesis. We have analyzed the function of the Drosophila Polycomb-Group gene polyhomeotic in epithelial cells of two different organs, the ovary and the wing imaginal disc.Clonal analysis of loss and gain of function of polyhomeotic resulted in segregation between mutant and wild-type cells in both the follicular and wing imaginal disc epithelia, without excessive cell proliferation. Both basal and apical expulsion of mutant cells was observed, the former characterized by specific reorganization of cell adhesion and polarity proteins, the latter by complete cytoplasmic diffusion of these proteins. Among several candidate target genes tested, only the homeotic gene Abdominal-B was a target of PH in both ovarian and wing disc cells. Although overexpression of Abdominal-B was sufficient to cause cell segregation in the wing disc, epistatic analysis indicated that the presence of Abdominal-B is not necessary for expulsion of polyhomeotic mutant epithelial cells suggesting that additional polyhomeotic targets are implicated in this phenomenon.Our results indicate that polyhomeotic mutations have a direct effect on epithelial integrity that can be uncoupled from overproliferation. We show that cells in an epithelium expressing different levels of polyhomeotic sort out indicating differential adhesive properties between the cell populations. Interestingly, we found distinct modalities between apical and basal expulsion of ph mutant cells and further studies of this phenomenon should allow parallels to be made with the modified adhesive and polarity properties of different types of epithelial tumors

Direct and long-range action of a wingless morphogen gradient.

Wingless (Wg), a founding member of the Wingless/Int-1 (Wnt) family of secreted proteins, acts as a short-range inducer and as a long-range organizer during Drosophila development. Here, we determine the consequences of ectopically expressing (i) a wild-type form of Wg, (ii) a membrane-tethered form of Wg, and (iii) a constitutively active form of the cytosolic protein Armadillo (Arm), which normally acts to transduce Wg, and we compare them with the effects of removing endogenous Wg or Arm activity. Our results indicate that wild-type Wg acts at long range, up-regulating the transcription of particular target genes as a function of concentration and distance from secreting cells. In contrast, tethered Wg and Arm have only short-range or autonomous effects, respectively, on the transcription of these genes. We interpret these findings as evidence that Wg can act directly and at long range as a gradient morphogen during normal development

Proximal–distal axis formation in the Drosophila leg

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