Factors Involved In Cell Differentiation

During cell differentiation in multicellular organisms, cells become specialized and take on roles such as those of nerve, muscle and blood cells. Factors involved in triggering cell differentiation include cell signaling, environmental influences and the level of development of the organism.

Basic cell differentiation occurs after a sperm cell fertilizes an egg and the resulting zygote reaches a certain size. At that point the zygote starts developing different cell types and needs differentiated cells to take on the specialized functions.

The mechanism that is at the root of cell differentiation is gene expression. All the cells of an organism have identical sets of genes because the genetic code was copied from the original egg cell fertilized by the sperm cell. To take on a specialized function, a cell will only express or use some of the genes in its genetic code and ignore the rest.

For example, a cell that differentiates to become a liver cell will express the liver cell genes, and all the other liver cells will use the same set of liver genes. They will differentiate together to form the liver.

Cell differentiation takes place in three situations:

• The growth of an immature organism into an adult.
• Normal turnover of cells such as blood cells in mature organisms.
• The repair of damaged tissues when specialized cells have to be replaced.

In each case, cell signaling informs cells what type of specialized cell is required. Undifferentiated cells express the corresponding genes to fulfill the needs of the organism.

The genetic code of eukaryotic cells is located on the DNA in the nucleus. The DNA can't leave the nucleus so the cell has to copy the gene it wants to express.

Messenger RNA (mRNA) attaches to the DNA and copies the relevant gene. The mRNA can travel outside the nucleus and bring the genetic instructions to ribosomes that are floating in the cell cytoplasm or that are attached to the endoplasmic reticulum. The ribosomes produce the protein encoded by the expressed gene.

Depending on the signals received by the cell, the environmental influences and the developmental stage of the cell, the process of gene expression can be blocked at any stage. If the protein encoded by the gene is not needed by the organism, the mRNA will not copy the gene, and the gene expression process will not start.

Even after the mRNA copies the gene, the mRNA molecule may be blocked from exiting the nucleus or may not be able to reach a ribosome. Ribosomes may not produce the required protein even if mRNA delivers the copied genetic code. Different factors can influence gene expression all through this multi-step process.

Organisms have several ways of ensuring that cells develop into the specialized and differentiated cells needed.

The key factor driving cellular differentiation in the body is the manufacture of proteins. Cells can differentiate depending on which genes are expressed and which proteins are encoded in the expressed genes. The produced proteins help the differentiated cells perform their specialized function and let them tell other cells what they are doing through cell signaling.

A further mechanism that can influence cell differentiation is asymmetric segregation in cell division. Substances such as special proteins gather at one end of a cell. When the cell divides, one daughter cell has more of the special proteins than the other. The cells become different types of cells due to the different protein distribution.

As a cell differentiates, the type of specialization it can take on becomes more limited. Embryonic stem cells can initially become any type of cell, but once the cell is mature and has taken on a specialized role, it often can no longer change. Embryonic stem cells are called totipotent cells because they can still take on any role while mature, specialized cells that are fully differentiated can only carry out their specialized function.

Gene expression is responsible for cell specialization, but the basic cells have to be able to take on the specialized functions. Before differentiation and cell specialization can take place, the right type of cell has to be available. Asymmetric segregation can produce such different types of cells. Totipotent embryonic cells become one of three types of pluripotent cells that eventually differentiate into the various body tissues.

The three types of pluripotent cells are:

• Endoderm cells become the lining of the respiratory and digestive tracts as well as forming the liver and many of the major glands such as the pancreas.
• Mesoderm cells differentiate to form muscles, bones, connective tissue and the heart.
• Ectoderm cells form the skin and nerves.

While cell signaling is responsible for the production of some different cell types and for cell specialization, asymmetric segregation acts at the beginning of cell development to produce pluripotent cells.

DNA transcription to mRNA takes place in such as way that the mRNA produces certain proteins at one end of the cell and different proteins at the other end. Cell division results in two different types of daughter cells that can go on to produce cells with different specializations.

Internal mechanisms that influence the cell differentiation of pluripotent cells are mainly based on cell signaling. Cells receive chemical signals that tell them what type of cell or what kind of protein is needed.

Cell signaling mechanisms include:

• Diffusion, in which cells release chemicals that spread throughout the tissues.
• Direct contact, in which cells have special chemicals on their cell membranes.
• Gap junctions, in which signaling chemicals can pass directly from one cell to another.

Cells continuously send out chemical messages regarding their activities and receive signals about what is going on in their immediate neighborhood, in the tissues where they are located and in the body at large. These signals are the principal factors that affect cell specialization, and cell signaling is the key factor driving cell differentiation in the body.

Cells become sensitive to certain chemical signals because they have receptors on their cell membrane. The receptors depend on the type of cell, how it has developed and which genes are being expressed. As receptors are activated, the cell differentiates further.

When a cell sends a signal to many nearby cells, it emits a chemical that diffuses through the tissue in which the cell is embedded. The chemical signal is captured by receptors in the cell membranes of the surrounding cells and triggers a response inside each cell. These responses help cause the cells to differentiate in a way that builds tissue.

For example, cells that will become part of a liver emit chemicals that trigger the corresponding receptors in nearby cells, and all the cells in that location differentiate to become liver cells. As the liver tissue forms, further cell signaling triggers some cells to differentiate into duct cells or connecting tissue. Eventually the differentiated cells form a complete and functional liver.

To develop into the specialized cells needed by the organism, cells have to know what other cells in their immediate surroundings are doing. Special receptors for cell-to-cell contact and gap junctions between cells facilitate the direct exchange of signals between neighboring cells. Cells can ensure that their surroundings correspond to their differentiated specialization.

In cell-to-cell signaling, specially formed receptor proteins on the surface of a cell match corresponding proteins on a neighboring cell's membrane. When the cells come into contact, the two proteins link, and a signal is triggered from one cell to the other. The signal passes through the cell membrane and enters the cell where it causes a specific cell behavior.

For example, skin cells have to make sure they have other skin cells around them, but some skin cells will have the cells of the underlying tissue beneath them. Cell-to-cell signaling lets cells ensure that their surroundings match their differentiation.

Gap junctions are special links between neighboring cells that allow an easy and direct exchange of proteins acting as messages. Using gap junctions, cells can coordinate their activities and exchange signals quickly and easily.

For example, nerve cells use gap junctions to establish nerve pathways, and gap junctions let cells differentiate into the type of nerve cell that is appropriate to their location in the skin, in the spinal cord or in the brain.

Cell signaling and the resulting cell differentiation are complex processes with many steps. Signals have to be produced, propagated received and acted upon. Triggers resulting from cell signals have to work as expected. Factors that disrupt any of the steps can influence cell differentiation and cause changes in the organism.

Factors that can influence and disrupt cell signaling and cell differentiation include a lack of nutrients; if a cell can't produce a protein because it lacks the building blocks, it can't differentiate. Mutations in the genetic code are another problem.

If the DNA is defective or the transcription is wrong, the signaling and differentiation process is disrupted. In addition to these, if the signaling chemicals are blocked or the cell receptors are filled with non-signaling chemical bonds, the signaling process will not work properly.

Influences from the environment of the organism that can affect cell signaling, gene expression and cell differentiation can change, stop or disrupt the process. Some environmental factors are used by the organism for adaptation, some can be used to fight disease and some harm or kill the organism.

For example, environmental temperature can influence the development of some organisms. Higher temperatures speed up the growth of cells and their differentiation while low temperatures slow down or stop development.

Drugs can disrupt harmful cell differentiation. For example, drugs can block one of the process steps for unlimited tumor growth and stop the expression of the corresponding genes.

Injuries can affect gene expression and influence what type of cell is needed to repair damage. Viruses and bacteria can influence cell differentiation. For example, if a mother is infected with a disease such as rubella, the developing fetus can have its cell differentiation influenced, and it can develop birth defects.

Finally toxic chemicals can affect cell differentiation. Substances that attack or block signaling chemicals or that block signal receptor positions on cell membranes can stop signaling activity and influence cell differentiation.

In the case of these environmental factors, the organism tries to respond by adapting or by changing internal processes. Adaptation is effective for some of the environmental influences, but for others, the organism may survive but exhibit defects, or the organism may die.