UNLABELLED According to morphogen gradient theory, extracellular ligands produced from a localized source convey positional information to receiving cells by signaling in a concentration-dependent manner. How do morphogens create concentration gradients to establish positional information in developing tissues? Surprisingly, the answer to this central question remains largely unknown. During de...

A long standing question in developmental biology is how morphogen gradients establish positional information during development. Although the existence of gradients and their role in developmental patterning is no longer in doubt, the ability of cells to respond to different morphogen concentrations has been controversial. In the Drosophila wing disc, Hedgehog (Hh) forms a concentration gradie...

The theory that the spatial organization of cell fate is orchestrated by gradients of diffusing molecules was a major contribution to 20th century developmental biology. Although the existence of morphogens is no longer in doubt, studies on the formation and function of their gradients have yielded far more puzzles than answers. On close inspection, every morphogen gradient seems to use a rich ...

How morphogen gradients govern the pattern of gene expression in developing tissues is not well understood. Here, we describe a statistical thermodynamic model of gene regulation that combines the activity of a morphogen with the transcriptional network it controls. Using Sonic hedgehog (Shh) patterning of the ventral neural tube as an example, we show that the framework can be used together wi...

Despite substantial size variations, proportions of the developing body plan are maintained with a remarkable precision. Little is known about the mechanisms that ensure this adaptation (scaling) of pattern with size. Most models of patterning by morphogen gradients do not support scaling. In contrast, we show that scaling arises naturally in a general feedback topology, in which the range of t...

Morphogens regulate tissue patterning through their distribution in concentration gradients. Emerging research establishes a role for specialized signalling filopodia, or cytonemes, in morphogen dispersion and signalling. Previously we demonstrated that Hedgehog (Hh) morphogen is transported via vesicles along cytonemes emanating from signal-producing cells to form a gradient in Drosophila epit...

I is known that several classes of signaling molecules stimulate complex concentration-dependent responses that are critical for growth, development, and tissue formation in multicellular organisms. 4,11 In recent years there have been many quantitative studies that revealed important features and details of morphogen gradients in different biological systems. 10 However, fundamental mechanisms...

In a classical view of development, a cell can acquire positional information by reading the local concentration of a morphogen independently of its neighbors. Accordingly, in Drosophila, the morphogen Wingless produced in the wing's prospective distal region activates target genes in a dose-dependent fashion to organize the proximodistal pattern. Here, we show that, in parallel, Wingless trigg...

Positional specification by morphogen gradients is traditionally viewed as a two-step process. A gradient is formed and then interpreted, providing a spatial metric independent of the target tissue, similar to the concept of space in classical mechanics. However, the formation and interpretation of gradients are coupled, dynamic processes. We introduce a conceptual framework for positional spec...

A fundamental and unresolved problem in animal development is the question of how a growing tissue knows when it has achieved its correct final size. A widely held view suggests that this process is controlled by morphogen gradients, which adapt to tissue size and become flatter as tissue grows, leading eventually to growth arrest. Here, we present evidence that the decapentaplegic (Dpp) morpho...