Biomedical subjects

Laurence Dubois

Publications and source records attributed to Laurence Dubois.

3 recordsLinked to original sources

PubMed2005

Arrow (LRP6) and Frizzled2 cooperate to degrade Wingless in Drosophila imaginal discs.

Lysosome-mediated ligand degradation is known to shape morphogen gradients and modulate the activity of various signalling pathways. We have investigated the degradation of Wingless, a Drosophila member of the Wnt family of secreted growth factors. We find that one of its signalling receptors, Frizzled2, stimulates Wingless internalization both in wing imaginal discs and cultured cells. However, this is not sufficient for degradation. Indeed, as shown previously, overexpression of Frizzled2 leads to Wingless stabilization in wing imaginal discs. We show that Arrow (the Drosophila homologue of LRP5/6), another receptor involved in signal transduction, abrogates such stabilization. We provide evidence that Arrow stimulates the targeting of Frizzled2-Wingless (but not Dally-like-Wingless) complexes to a degradative compartment. Thus, Frizzled2 alone cannot lead Wingless all the way from the plasma membrane to a degradative compartment. Overall, Frizzled2 achieves ligand capture and internalization, whereas Arrow, and perhaps downstream signalling, are essential for lysosomal targeting.

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PubMed2003

[Morphogens and endocytosis].

During development, secreted signaling proteins of the Wingless/Wnt, Hedgehog and Decapentaplegic (Dpp)/Bone Morphogenic Protein (BMP) families act as morphogens. Previous work had shown that these molecules act directly on distant cells, although until recently nothing was known about how they reach those distant cells. During the past two years, work carried out on Drosophila using genetic and cell biology approaches have revealed that endocytosis plays a central part in the mechanisms that control the spread of morphogens.

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PubMed2002

Morphogen transport along epithelia, an integrated trafficking problem.

Graded signals are an important component of current models of pattern formation. Typically, a group of cells produces a signal that decays as it spreads through neighboring tissue. By contrast with endocrine signals, which spread systemically, patterning signals or morphogens have a restricted zone of influence, an area classically known as a field. The widely accepted model is that graded distribution of such signals allow cells to measure their position relative to the source. Although it provides a framework for understanding pattern formation, the concept of the morphogen raises many mechanistic issues. For example, how the distribution of a morphogen is established and maintained remains an outstanding issue. There is no doubt that signals are transported over distances of tens of cell diameters and that stable gradients do form. The question of how this is achieved has aroused the interest of many cell biologically minded developmental biologists.

Animals↗