Moving the molecules that control embryo development

How do the molecules that regulate embryo development end up in the right place at the right time? We examined several current theories and suggest that diffusion-based mechanisms are the most commonly used during development.

HFSP Career Development Award holder Patrick Müller and colleagues
authored on Thu, 23 May 2013

Animals begin life as a single cell that divides to give rise to a multicellular embryo. Embryonic cells are initially equal, but they eventually specialize into different cell types such as muscle or nerve cells. These cell fate decisions are triggered by instructional molecules called morphogens, which form concentration gradients in the embryo (see figure). Cells sense the morphogen and choose different fates based on the concentration of morphogen they encounter. Morphogen gradients are therefore important to ensure that animals will have the appropriate number of different cell types in the right place.

How do morphogen gradients form? Morphogens are often produced by a small set of cells within the embryo. Gradients form because molecules move away from this source. The mechanism by which morphogens move is controversial and may depend on the morphogen type, developmental context, and species. For example, it has been suggested that morphogens move by a process called transcytosis in which cells take in and expel morphogen molecules, thereby passing them from cell to cell and eventually transporting them away from the source. Alternative mechanisms in which cells use straw-like projections to “suck up” morphogen and move it away from the source have also been proposed.

Figure: Morphogens form concentration gradients that dictate the fate of cells. If morphogen gradients do not form properly, the wrong number of cell types is made.

Using mathematical modeling, experimental measurements, and re-analysis of existing data, we found that most evidence supports the idea that morphogens move through embryos by diffusion-based mechanisms. Diffusion is the random movement of a molecule through a medium, analogous to a drunken person stumbling around aimlessly. In the simplest scenario, morphogen is produced by the source cells and pumped into the space that surrounds the cells. Morphogen molecules diffuse in this extracellular space, and over time a gradient of morphogen is formed with the highest concentration near the source. Many additional factors can influence the range of gradients formed by diffusion, including the stability of morphogens and binding interactions with other molecules in the extracellular space. Morphogen gradients are thereby generated that allow embryonic cells to make the correct cell fate decisions in the right place at the right time.

Text by Patrick Müller and Katherine Rogers

Reference

Morphogen transport. Müller P, Rogers KW, Yu SR, Brand M, Schier AF. Development. 2013 Apr;140(8):1621-38. doi: 10.1242/dev.083519.

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