Understanding morphogen gradients: a problem of dispersion and containment

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Protein morphogens are instructive signals that regulate growth and patterning of tissues and organs. They form long-range, dynamic gradients by moving from regions of high concentration (producing cells) to regions of low concentration (the adjacent, nonproducing developmental field). Since morphogen activity must be limited to the adjacent target field, we want to understand both how signaling proteins move and how their dispersion is restricted. We consider the variety of settings for long-range morphogen systems in Drosophila. In the early embryo, morphogens appear to disperse by free diffusion, and impermeable membranes physically constrain them. However, at later stages, containment is achieved without physical barriers. We argue that in the absence of constraining barriers, gradient-generating dispersion of morphogens cannot be achieved by passive diffusion and that other mechanisms for distribution must be considered.

Introduction

Concentration gradients of protein morphogens are thought to embody the informational landscapes that regulate and pattern developmental fields. As a function of either absolute or relative concentration, they elicit differential responses across a field of target cells. Most of these gradients form by dispersion from a localized source, and their activity is transmitted through widely distributed receptors. Although morphogen movement has been studied intensively and has been the subject of numerous excellent reviews (recent ones include [1, 2, 3, 4, 5, 6, 7]), neither experimental nor theoretical analysis has established the mechanisms that distribute these proteins across developmental fields. This review focuses on an aspect of morphogen gradients that has received little attention — the means by which morphogen movement is limited. It examines morphogen gradients in the Drosophila oocyte, precellular embryo, and wing imaginal disc, and argues that the architecture of the oocyte, embryo, and disc bears directly on the manner by which morphogens are restricted to their intended targets. These considerations have significant implications for the possible mechanisms that disperse morphogens in these different settings.

Section snippets

Gradient systems of the Drosophila oocyte and embryo

Several aspects of the morphogen gradients that organize the Drosophila oocyte and embryo are unique. First, the proteins that form instructive concentration gradients at these developmental stages are not employed again as morphogens at later developmental stages. Second, the concentration gradients signal in three-dimensional space, either from one cell layer to another or across the volume of the embryo. Third, although their concentration profiles are controlled in part by kinetics of

Gradient systems of the Drosophila wing imaginal disc

The morphogens that pattern organ systems during embryogenesis and larval development operate in settings that differ from those of the precellular Drosophila embryo. We will focus this discussion on the wing primordium of the wing imaginal disc. The protein morphogens that regulate the wing primordium appear to play similar roles in many different vertebrate and invertebrate organs, and if we assume that the mechanisms that disperse these morphogens are also conserved in these other settings,

Movement of signaling proteins in the wing disc

The transparency of the Drosophila basal lamina to FGF signaling contrasts with the barrier functionality of the embryo plasma and vitelline membranes. The question arises whether transparency is a general property of basal lamina — whether the basal lamina is also transparent to Hh, Dpp, and Wg. No measures of Hh, Dpp, or Wg signaling through basal lamina have been reported, but if basal lamina were not transparent, it would presumably bind these proteins to restrict their movement. FGF binds

Concluding remarks

There are two types of environments in which morphogen signaling gradients communicate information. One type is represented in the Drosophila oocyte and precellular embryo. At these developmental stages, although the different signaling proteins are produced and function in a variety of ways, they each appear to disperse to form informational gradients by passive diffusion, either within the confines of the narrow space that surrounds the oocyte and embryo or within the syncytial cytoplasm of

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

We thank members of our lab as well as our colleagues Gail Martin, Didier Stainier, Jeremy Reiter, and Chester Chamberlain for helpful comments on the manuscript, and we acknowledge the National Science Foundation and the National Institutes of Health for funding.

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