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From signaling molecules to transcription factors and gene expression, in this lesson you’ll learn what it takes for a cell to differentiate.

You’ll also learn some of the ways a cell can make sense of different combinations of signaling molecules and how these combinations can be used to guide a cell through the process of differentiation.

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Differentiation

Differentiation is the process by which a cell becomes a functional, mature cell of a specific type. As you may remember, signaling molecules play a key role in the differentiation of different cell types in the developing embryo. But how do they actually work? A cell doesn’t just automatically differentiate when it encounters a signaling molecule. It’s quite a bit more complicated than that, and for good reason, too.

With hundreds of potential signaling molecules that a cell could encounter, it has to be able to respond to a real signal and ignore a chance encounter with a stray molecule.In addition, the cell has to incorporate information from more than one type of signaling molecule in order to activate the correct differential program. And then there is the question of what changes in a cell that causes it to differentiate. So buckle up and get ready, because we’re going on a whirlwind tour of what causes a cell to differentiate!

Ligands and Receptors

Let’s use BMP-4 again as an example of a signaling molecule. In biology terms, BMP-4 is considered to be a ligand, or a molecule that binds to a receptor.

BMP-4 is able to specifically bind to a BMP receptor; however, one BMP-4 molecule binding to one BMP receptor is not enough to signal the cell. In this case, it takes two BMP-4 molecules bound to four BMP receptors to activate a signaling pathway within the cell. This is fairly typical for receptor signaling in cells.You see, if it only took one ligand bound to one receptor to activate a signaling pathway, then one stray, out-of-place signaling molecule or one defective receptor bound to the wrong ligand could potentially activate the wrong signaling pathway. By requiring more than one signaling molecule to form a complex with more than one receptor, the cell ensures that the signaling molecule is available in abundance and that it can be recognized by multiple receptors.When the required number of ligands binds to the required number of receptors, a signaling pathway is activated inside the cell.

These pathways are composed of a series of molecules, mostly proteins and lipids, that alter each other in a specific sequence and ultimately lead to the activation of a type of protein called a transcription factor.

A signaling pathway leading to the activation of a transcription factor
Transcription Factor Activation

Transcription Factors

A transcription factor is a protein that can bind to a specific DNA sequence and activate transcription of a gene.

Each transcription factor has a unique DNA sequence that it recognizes and binds to called a transcription factor binding site. Sounds simple enough – a transcription factor binds to its binding site and activates transcription of a gene, right?Well, not so fast. You see, one transcription factor alone isn’t sufficient to activate transcription of a gene. Usually it takes three or more different transcription factors all binding to their specific transcription factor binding sites in close proximity to each other to activate transcription of a nearby gene. This is one way that multiple signaling pathways activated by multiple signaling molecules can be integrated together to direct a very specific set of genes to be transcribed.Let’s take a look at how this can happen. Let’s say that we have an embryonic cell that is in a location where three different signaling molecules are concentrated enough to activate their specific receptors and activate their signaling pathways.

For simplicity’s sake, we’ll give these signaling molecules the generic names A, B and C. Let’s also say that the signaling pathways activate transcription factors named TF-A, TF-B and TF-C, which bind to specific DNA sequences that we’ll designate as binding sites A, B and C respectively.

Example of the transcription factor activation process
Diagram of Transcription Activation

In this example, transcription factors TF-A, TF-B and TF-C will all be activated and can bind to binding sites A, B and C, which are scattered throughout the genome.

In very specific areas where all three of these binding sites are located close enough together, the transcription factors can work together to initiate transcription of a nearby gene. Often, several genes will have the same group of binding sites nearby and will all be transcribed as a result of the same combination of signaling molecules. However, a gene that is regulated by a combination of hypothetical transcription factors TF-B, TF-C and TF-D will not be transcribed because the combination of just TF-B and TF-C bound to the nearby DNA is not enough to activate transcription of the gene.

In this way, the specific combination of signaling molecules A, B and C can together activate transcription of a number of genes that can cause the cell to differentiate into a specific cell type. Alternatively, in another cell that is exposed to signaling molecules A, B and D, a totally different set of genes will be transcribed and the cell will differentiate into a different type of cell.In many cases, genes that are transcribed as a result of these signaling molecules are themselves transcription factors that can combine to activate subsequent rounds of transcription of a completely different set of genes. By transcribing and eventually expressing new sets of transcription factors at different times, a cell can differentiate in stages over time.

Gene Expression

Gene expression, or the formation of a protein encoded by a particular gene, is extremely important during development.

This is because, at the most fundamental level, what makes a brain cell different from a liver cell is the genes that they express. For the most part, every cell in your body has the same DNA that makes up the entire human genome. This means that, with only a few exceptions, every type of human cell has all of the genes that encode all of the proteins found in the entire body.

A brain cell does contain genes that encode for proteins that are only found in liver cells, and liver cells do contain genes that encode for proteins that are only found in brain cells, but each type of cell in the human body only expresses the genes it needs to function properly and do the specific job it is supposed to do. As a result, signaling molecules and the transcription factors that they activate play a critical role in the differentiation of cell types.Scientists don’t yet know all of the signaling molecules, transcription factors and other molecules that are needed to express every human gene, but they’re working on it. Who knows – maybe someday we’ll even have ways to manipulate gene expression in patients who could benefit from regulating the expression of certain genes.

Lesson Summary

Let’s review. A ligand is a molecule that binds to a receptor. Most signaling molecules, like BMP-4, are ligands and can bind to receptors located on the surface of a cell.

However, it takes two BMP-4 molecules bound to four BMP receptors to activate a signaling pathway within the cell. This ensures that the signaling molecule is available in abundance and it can be recognized by multiple receptors.When the required number of ligands binds to the required number of receptors, a signaling pathway is activated inside the cell.

For signaling molecules that regulate development, the end result of an activated signaling pathway is usually the activation of a specific transcription factor.A transcription factor is a protein that can bind to a specific DNA sequence and activate transcription of a gene. Each transcription factor has a unique DNA sequence that it recognizes and binds to called a transcription factor binding site.

Usually it takes three or more different transcription factors all binding to their specific transcription factor binding sites in close proximity to each other to activate transcription of a nearby gene. This is one way that multiple signaling pathways activated by multiple signaling molecules can be integrated together to direct a very specific set of genes to be transcribed.A gene is transcribed if the correct combination of transcription factors binds to their specific binding sites in a cluster that is in close proximity to the gene.

In this type of system, slightly different combinations of active transcription factors in a cell can result in completely different sets of genes that are transcribed.Differentiation is the process by which a cell becomes a functional mature cell of a specific type. One of the most important components of differentiation is gene expression, or the formation of a protein encoded by a particular gene. This is because, at the most fundamental level, what makes a brain cell different from a liver cell is the genes that they express.For the most part, every cell in your body has the same DNA that makes up the entire human genome.

However, each type of cell in the human body only expresses the genes it needs to function properly and do the specific job it is supposed to do. As a result, signaling molecules and the transcription factors that they activate control gene expression and, ultimately, differentiation.

Learning Outcomes

After watching this lesson, you should be able to:

  • Define differentiation, ligand, transcription factor and transcription binding site
  • Summarize the process of transcription factors signaling transcription pathways in cells
  • Explain gene expression and how a brain cell is different from a liver cell

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