Cellular Differentiation Part I: The Cell Cycle During your lifetime, trillions of your cells will undergo the cell cycle. This process allows you to grow, heal, and maintain your vital tissues and organs. In order for organisms to grow and thrive, certain cells must constantly undergo mitosis, such as the skin and stomach cells in animals. The process of creating new cells is part of the cell cycle, or a series of events that a eukaryotic cells undergoes in order to divide and replicate. The cell cycle may renew other somatic cells, or nonreproductive cells, in the body. The entire cell cycle can be divided up into four different phases: Gap 1 (G1), Synthesis (S), Gap 2 (G2), and the Mitotic Phase (M). The M Phase includes both mitosis and cytokinesis. Interphase Interphase is the first stage of the cell cycle, and the longest phase. The cell undergoes normal functioning and growth during this phase. DNA is replicated in preparation for the cell to divide. Interphase is broken into three phases: G1 Phase, Synthesis (S) Phase, and G2 Phase. G1 Phase of Interphase Here the cell is in a phase where it grows in size, but is not duplicating any genetic material. S Phase of Interphase During this phase the genetic material, or DNA, of the cell is duplicated. In this phase, the DNA is in the form of chromosomes. G2 Phase of Interphase This is the phase where the cell prepares for division. Centrosomes are formed during this phase. These structures aid in later phases of cellular division. Please continue to the next page. 1
Part I: The Cell Cycle, continued Mitosis After a cell has moved through all three phases of interphase, it is ready to begin the process of mitosis, or the process of nuclear division to form two distinct nuclei. This process occurs in the following four steps: Prophase During the first phase of mitosis, the loosely bundled DNA begins to condense by coiling tightly into more organized sister chromatids, which are joined by a protein bundle called a centromere. During prophase, the chromosomes are visible under a light microscope. In late prophase, the nuclear membrane breaks into fragments and disappears, freeing the genetic contents of the nucleus. In the cytoplasm, microtubules grow from the centrosomes. The cell s two centrosomes begin moving toward the opposite ends of the cell. Chromatids Centrosomes Centromeres Metaphase During metaphase, the centromeres of each chromosome line up in the center of the cell, known as the metaphase plate. The centrosomes are at opposite poles and are connected to the centromeres by spindle fibers that are made up of microtubules and proteins. Some microtubules connect opposite centrosomes and are used to create a pushing force during cell division. Metaphase Plate Please continue to the next page. 2
Cellular Differentiation Part I: The Cell Cycle, continued Anaphase This third phase of mitosis begins when the two centromeres of each chromosome part ways and separate the sister chromatids. Each chromatid is now considered a complete chromosome. Microtubules connected to the centromeres shorten, pulling the chromosomes toward the opposite poles of the cell. Microtubules not connected to centromeres elongate, pushing the poles further apart. When anaphase ends, there is a complete set of chromosomes at each pole of the cell. Telophase/Cytokinesis During telophase, the cell begins to elongate, and a membrane forms around the two sets of chromosomes. The chromosomes begin to uncoil and nucleoli reappear in each nucleus. Cytokinesis, or the division of cytoplasm, begins during telophase. In animal cells, a cleavage furrow forms where the metaphase plate used to be. This cleavage furrow pinches together until two new daughter cells are formed with identical copies of DNA. In plant cells, a new cell wall grows at the site of the metaphase plate until the two daughter cells are separated. When cytokinesis is complete, the two new daughter cells begin their own cell cycles. Complete Part I of your Student Journal. 3
Part II: Cell Cycle Regulation There are several factors responsible for regulating the cell cycle. DNA contains many different genes that produce specific proteins. Some proteins called cyclins control different phases of the cell cycle. Cyclins, in turn, are regulated by another class of proteins known as growth factors. Some growth factors trigger cyclins that cause cells to divide, while others stop cell growth by blocking the action of cyclins. Cells also have specialized proteins that check the DNA for sequence errors during replication. Some errors, or mutations, can be repaired. If too many mutations are identified, cells don t progress through the cell cycle. Cell growth and division can also be affected by contact inhibition. When a cell is in close contact with other cells, proteins are produced that cause cells to remain in the G 1 phase. If you sustain a cut or scrape on the skin, proteins are produced promoting cell growth. Cells in the damaged area will begin to divide until the wound is healed, when contact inhibition again triggers cells to remain in the G 1 phase. In fact, there is something called the G 1 checkpoint, or the restriction point. If the cell is not properly signaled to divide at the G 1 checkpoint, the cell will move into a G 0 phase where it does not divide at all. Most somatic cells in animals exist in the G 0 phase, as once developed they won t (usually) divide again. The cell cycle also plays a role in what is known as cellular differentiation. As you already know, your body is a collection of many different cell types. In animals, stem cells are unspecialized cells that are constantly reproducing, especially during the growth and development phases of the animal. These cell types have the ability to differentiate in many different types of cells based on both internal and external signals. Complete Part II of your Student Journal. 4
Part III: Specialized Cells As animals grow and develop, the stem cells differentiate into more and more specific and specialized cell types. These specialized cells may be found only in certain areas of the body, such as in epithelial or bone cells, or may be found throughout the body, such as blood cells in the circulatory system. Some of the very specific types of cells found in animals include blood cells, muscle cells, epithelium cells, bone cells, and nerve cells. Blood cells are specialized cells that are suspended within plasma in the blood of animals. These types of cells may carry oxygen throughout the body or fight infections. There are two types of blood cells. White blood cells are called leukocytes and they fight infection. Red blood cells are called erythrocytes and carry oxygen through the body. Epithelial cells make up the epithelial tissues of the body, and there are many different types. Epithelial cells include skin cells, as well as the lining of many organs and organ systems, such as the lining of the lungs or the digestive tracts. Muscle cells may fall into three categories. Smooth muscle cells are spindle shaped and are found in organs. Skeletal muscle is made of long fibers that are bundled into structures called myofibrils. Cardiac muscles are found in the heart and are connected to synchronize a heartbeat. There are a variety of connective tissues that each have their own cell type. These tissues include bone cells, cartilage, connective tissues, and fat cells. Nerve cells, or neurons, are a major component of the nervous tissues. These types of cells transmit electrical signals between any part of the body and the brain. Many neurons are connected to either muscle or connective tissues. Complete Part III of your Student Journal. 5
Part IV: DNA, RNA, and Differentiation So what controls how cells know to differentiate into a wide variety of specialized cells? It has to do with the genetic material contained within each cell. Remember that during interphase in somatic cells, the cells are growing and the DNA is being duplicated. Then, at some point there is a signal to start the replication process, usually at the G 1 checkpoint. It is at this point that the genetic material, or DNA, of each cell is triggered to do work. Every single cell in your body contains the exact same copy of DNA as every other cell. That DNA contains individual sections called genes. There are genes that will code for specific proteins. It is these genes found on the DNA strands that will determine whether a cell becomes a skin cell or a nerve cell. So how exactly does this occur? All of the cells within an organism are constantly sending signals to each other. It is these specific signals that turn on certain genes along the DNA strand. As the DNA is replicated, or transcribed, it is read by another form of genetic material known as RNA. The RNA will, in turn, synthesize the specific proteins coded for on the DNA strand. It is these proteins that determine what type of cell it will become. In other words, each gene found on the DNA codes for its own protein. As the RNA reads each gene, the information contained in the DNA segment is then translated by the RNA. The RNA then uses this translation to build a protein. For example, cells in the interior of the body will be signaled by genes to become either muscle or connective tissues, while other cells on the exterior of the body will be signaled to become epithelial cells. This process is known as gene expression. As you can imagine, any errors, or mutations, to the gene may cause errors in the translation process. These errors may lead to a variety of disorders and diseases. GENE EXPRESSION DNA (gene is signaled) à RNA à Protein Synthesis à Muscle Cell Complete Part IV of your Student Journal. 6
Part V: Disruptions in the Cell Cycle As you can imagine, if regulatory checks or signals fail, cells can grow and divide without restraint. For example, if the go signal is not given at the G 1 checkpoint, but the cell begins to divide anyway, this can lead to the rapid an unregulated growth of somatic cells that might otherwise remain in the G 0 phase. The result can be a mass of cells that known as a tumor. Some tumors may show unregulated growth, but they do not spread to other parts of the body. These types of tumor are known as benign tumors, and once removed do not return. Other tumors may continue to grow and invade other tissues, or may break away and spread to other parts of the body. These are known as malignant tumors, and are associated with cancer. Cancer refers to a specific class of disease caused by unregulated cell growth. Cancer cells do not respond to normal signals to stop growth and reproduction. Sometimes a mutation in a gene can be responsible for this type of disruption to the cell cycle. Mutated genes that cause cancer are known as oncogenes. The process by which normal cells are transformed into cancer cells is known as carcinogenesis, or oncogenesis. This transformation affects gene expression in that the genes responsible for normal cell division are mutated. However, it is important to note that more than one gene must mutate in order for carcinogensis to occur. Several related genes must undergo progressive mutations in order for a normal cell to transform into a cancer cell. The gene mutations that lead to cancer may be caused by many sources. Overexposure to UV rays from the sun may disrupt the cell cycle. Other environmental factors that may cause cancers by disrupting the cell cycle include carcinogens taken in by smoking, chemical exposures, and overexposure to X-rays. There are also certain viruses that have been linked to cancer causing tumors. Complete Part V of your Student Journal and then complete the Reflections and Conclusions. 7