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Concentration Gradients, Signaling Molecules & Inhibitors in Development

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  • 0:04 How Does Spemann's…
  • 1:51 Gradient Formation
  • 3:58 Multiple Concentration…
  • 5:08 Lesson Summary
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Lesson Transcript
Instructor: Joshua Anderson
The discovery and characterization of Spemann's organizer was a significant achievement in the field of developmental biology, but this small piece of the dorsal lip is only the tip of the iceberg when it comes to coordinating the differentiation of all of the various tissue types in a growing embryo. In this lesson, you'll learn about concentration gradients and how they can be used to create various combinations of signaling molecules in different parts of the embryo.

How Does Spemann's Organizer Work?

So you may remember that over a hundred years ago, Hans Spemann and Hilde Mangold showed that a particular part of the early embryo acted as an organizer and could determine the developmental fates of the cells around it. This dorsal lip of an amphibian gastrula that is capable of organizing the structures of the developing embryo was later named Spemann's organizer.

Diagram of Spemanns Organizer
Spemanns Organizer Diagram

Now, Spemann and Mangold didn't know exactly how this organizer worked, but they believed that it was using some sort of chemical to signal to the other cells and direct their development. Their belief turned out to be correct, or rather, mostly correct. Over a hundred years of research on the subject has resulted in the discovery of a very complex and intricate system of signaling molecules, inhibitors and proteases. Signaling molecules are molecules, usually proteins, that are used to send signals between different cells. Inhibitors are proteins that inhibit receptors and other proteins. And proteases are proteins that degrade other proteins.

Spemann's organizer is indeed the source of a number of different proteins that are involved in this complex regulatory system. However, it is not the only source of signaling molecules, inhibitors and proteases in the embryo. The entire signaling cascade of proteins involved in embryonic development is far too complex to adequately describe here. Even so, I can describe a very small portion of the system, which will give you an idea of how these different proteins can work together to help regulate pattern formation within the developing embryo.

Gradient Formation

In the early frog gastrula, one of the key developmental signaling molecules is BMP-4, which is produced in the ventral portion of the embryo. BMP-4 is a protein that is involved in the development of ventral structures. However, an inhibitor of BMP-4, called chordin, is produced in Spemann's organizer along with several other protein-specific inhibitors. Since BMP-4 is produced in the ventral portion of the embryo and its inhibitor, chordin, is produced in Spemann's organizer, the ventral portion of the embryo receives high doses of active BMP-4. At the same time, the high levels of chordin in the dorsal part of the embryo inhibit BMP-4 activity in this part of the embryo, which results in basically no BMP-4 signaling there.

The location of different proteins within the embryo creates a concentration gradient.
Concentration Gradient in Frog Gastrula

Yet another layer of regulation exists in the form of a protease, called Xolloid, which degrades chordin. Like BMP-4, Xolloid is produced in the ventral portion of the embryo. Xolloid helps to sharpen the concentration gradient of BMP-4 activity by degrading chordin in the ventral part of the embryo, where BMP-4 levels are already high. In the dorsal portion of the embryo, chordin is so abundant that the small amount of Xolloid that reaches this part of the embryo has little effect and chordin can still inhibit all BMP-4 activity.

Because of the locations of the sources of these different proteins and the ways that they interact with each other, they set up a concentration gradient along the dorsoventral axis. In this case, because of the interactions of inhibitors and proteases, the change in concentration occurs very quickly, so that in the ventral half of the embryo there is a high concentration of active BMP-4 and in the dorsal half of the embryo nearly all of the BMP-4 activity is inhibited.

Multiple Concentration Gradients Add Complexity

It should be noted here that not all concentration gradients transition this quickly. There are many other concentration gradients of different proteins that transition much more gradually. In these cases, very high concentrations of a protein may lead to one type of differentiation, medium concentrations may lead to a second type of differentiation and low concentrations may lead to a third type of differentiation. Then, if concentration gradients of other signaling molecules are layered on top of each other, additional complexity can be added and dozens of differentiation programs can be activated in different cells based on the combination of signaling molecule concentrations.

Varied protein concentration gradients affect the type of differentiation in cells.
Protein Concentrations Diagram

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