Critical Point in Self-Organized Tissue Growth

We present a theory of pattern formation in growing domains inspired by biological examples of tissue development. Gradients of signaling molecules regulate growth, while growth changes these graded chemical patterns by dilution and advection. We identify a critical point of this feedback dynamics, which is characterized by spatially homogeneous growth and proportional scaling of patterns with tissue length. We apply this theory to the biological model system of the developing wing of the fruit fly \textit{Drosophila melanogaster} and quantitatively identify signatures of the critical point.Comment: 5 pages, 3 figure

Control of proliferation by the Dpp gradient in the wing imaginal disc of Drosophila melanogaster

Morphogens, such as Decapentaplegic (Dpp) in the fly imaginal discs, form graded concentration profiles that control patterning and growth of developing organs. In the imaginal discs, proliferative growth is homogeneous in space, posing the question of how morphogen concentration gradients could control position-independent growth. To understand the mechanism of proliferation control by the Dpp gradient, we quantified Dpp concentration and signaling levels during wing disc growth. Both Dpp concentration and signaling gradients scale with tissue size during development. On average, cells divide when Dpp signaling levels have increased by 50%. Our observations are consistent with a growth control mechanism based on temporal changes of cellular morphogen signaling levels. For a scaling gradient, this mechanism generates position-independent growth rates

Growth control by a moving morphogen gradient during Drosophila eye development

During morphogenesis, organs grow to stereotyped sizes, but growth control mechanisms are poorly understood. Here, we measured the signaling dynamics of the morphogen Dpp, one of several Drosophila factors controlling morphogenetic growth, in the developing eye. In this tissue, the Dpp expression domain advances from the posterior to the anterior tissue edge. In front of this moving morphogen source, signaling inputs including Dpp activate the target gene hairy in a gradient that scales with tissue size. Proliferation, in turn, occurs in a mitotic wave in front of the source, whereas behind it, cells arrest and differentiate. We found that cells divide when their signaling levels have increased by around 60%. This simple mechanism quantitatively explains the proliferation and differentiation waves in wild type and mutants. Furthermore, this mechanism may be a common feature of different growth factors, because a Dpp-independent growth input also follows this growth rule

Morphogen Gradient Formation

How morphogen gradients are formed in target tissues is a key question for understanding the mechanisms of morphological patterning. Here, we review different mechanisms of morphogen gradient formation from theoretical and experimental points of view. First, a simple, comprehensive overview of the underlying biophysical principles of several mechanisms of gradient formation is provided. We then discuss the advantages and limitations of different experimental approaches to gradient formation analysis

Investigating the principles of morphogen gradient formation: from tissues to cells

Morphogen gradients regulate the patterning and growth of many tissues, hence a key question is how they are established and maintained during development. Theoretical descriptions have helped to explain how gradient shape is controlled by the rates of morphogen production, spreading and degradation. These effective rates have been measured using fluorescence recovery after photobleaching (FRAP) and photoactivation. To unravel which molecular events determine the effective rates, such tissue-level assays have been combined with genetic analysis, high-resolution assays, and models that take into account interactions with receptors, extracellular components and trafficking. Nevertheless, because of the natural and experimental data variability, and the underlying assumptions of transport models, it remains challenging to conclusively distinguish between cellular mechanisms

Dynamics of Dpp Signaling and Proliferation Control

Morphogens, such as Decapentaplegic (Dpp) in the fly imaginal discs, form graded concentration profiles that control patterning and growth of developing organs. In the imaginal discs, proliferative growth is homogeneous in space, posing the conundrum of how morphogen concentration gradients could control position-independent growth. To understand the mechanism of proliferation control by the Dpp gradient, we quantified Dpp concentration and signaling levels during wing disc growth. Both Dpp concentration and signaling gradients scale with tissue size during development. On average, cells divide when Dpp signaling levels have increased by 50%. Our observations are consistent with a growth control mechanism based on temporal changes of cellular morphogen signaling levels. For a scaling gradient, this mechanism generates position-independent growth rates