Rise of the Source-Sink Model

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Entry by Angelo Mao, AP 225, Fall 2010

Title: Rise of the source-sink model

Authors: Alexander F. Schier and Daniel Needleman

Journal: Nature

Volume: 461(24 September 2009)

Pages: 480-481

Summary

Cell signalling via gradients plays an important role in embryonic development. The authors suggest several different ways that this gradient is created and maintained, including extracellular diffusion and transport through cells. Recent studies enabled by technological developments in techniques such as fluorescent correlation spectroscopy (FCS) provide evidence for these different developmental regimes.

Soft Matter Keywords: in vivo, diffusion

Overview

Mao3 1 threekinds.jpg

Figure 1. Three different kinds of transport models.

The authors cited two studies that both focused on transport of morphogens. One study was by Yu et al. This study provided evidence for the transport model as being driven by diffusion and Brownian motion. Briefly, the morphogen Fgf8 of gastrulating zebrafish embryos was labeled with a green fluorescent protein (GFP). This allowed the researchers to track the location of the Fgf8 morphogen. The measured diffusion coefficient was around 53 <math>\mu m^{2} s^{-1}</math> and fit the diffusion model, though it did not fit other proposed models, such as active directed transport (figure 2). Therefore the creation of the Fgf8 morphogen was similar to what is shown on the top third of figure 1. Moreover, this model predicted how the gradient was maintained, which was by endocytosis of the morphogen by downstream cells. This created a "sink" that would keep the gradient sharp. The researchers altered the endocytosis of downstream cells as well as used other fluorescent markers to verify their findings.

Mao3 2 fit.jpg

Figure 2. Comparison of data obtained by FCS in comparison to models. The secEGFP data refers to GFP control, which is not labeled to the Fgf8 morphogen. The active transport model is a proposed model matching Figure 1 middle or bottom, and that did not fit the data for Fgf8.

The authors referred to the results of another study by Kicheva et al, in which the morphogen gradient did not seem likely to have been created by diffusion. Their model was the Decapentaplegic (Dpp) protein in Drosophila, and the technique they used, though similar in principle to FCS, was basically the reverse. In short, Kircheva et al bleached a region of the fly wing that had fluorescently labeled Dpp and tracked the time it took for Dpp molecules to re-enter the bleached area. The measured diffusion coefficient was about 0.1 <math>\mu m^{2} s^{-1}</math>, about three orders of magnitude smaller than that of Fgf8 in zebrafish embryo. The authors proposed that this was because transport of Dpp was governed by a different mechanism, perhaps transport through the inside of cells, as shown in figure 1, middle.

Conclusion

The authors considered two papers that asked similar questions: how were gradients of molecules formed and maintained in developing embryos? Aptly, the authors pointed out that the mechanisms were likely different, as that would explain the nonconformity of the results. They were also right in pointing out that there was a difference in size scale between the experiments done by Yu et al and Kicheva et al. In the former, FCS was directed at an area of 0.1 micron squared; in the latter, the area photobleached was about 10,000 microns squared. Diffusion as a transport mechanism would only be feasible over a certain size range. An unaddressed point between the two studies was the relative sizes of the two proteins Dpp and Fgf8. The question of appropriate length scale in the microscopic world is an apt one in soft matter dynamics.

References

Yu, S. R. et al. Nature 461, 533–536 (2009).

Kicheva, A. et al. Science 315, 521–525 (2007).