Apoptosis Learning outcome O Outline how apoptosis (programmed cell death PCD) can act as a mechanism to change body plans. Pages O Cells are not immortal. They can only undergo a limited number of cell division (usually about 50) and then die. It is not the type of death that is caused by damage or trauma,(necrosis) but an orderly series of events leading to cell death. This ordered or programmed cell death is called apoptosis (PCD Programmed cell death!) O Starter: What useful roles do you think apoptosis has in the human body??

Roles of apoptosis O Maintenance of adult cell numbers: adulthood about 10 billion cells die/made each day! O Defence against damaged or dangerous cells such as viral infected cells or cells with damaged DNA O Sculpting embryonic tissue during its development (fingers/toes/webs) PCD involves an orderly series of biochemical events, which is tightly controlled and results in set changes in cell morphology and end in cell death. O The process ensures safe disposal of cell remains.

3 Normal cell, capable of dividing for a number of cycles – the Hayflick constant, about 50 divisions. After this, a series of ordered steps results in the death of the cell – not the same as necrosis! Cell begins to break down. Enzymes digest the cytoskeleton and the cytoplasm becomes dense. The chromatin condenses and DNA fragments. Blebs (extrusions of the cytoplasm) appear containing cytoplasmic material. Cell shrinks as it disintegrates. The blebs containing cytoplasm and organelles are phagocytosed (engulfed) by phagocytes and digested. Process is quick and prevents damage to surrounding tissues (if necrosis, enzymes and toxic products can cause extensive damage). Apoptosis or programmed cell death

The series of events during apoptosis: O the cell membrane begins to bleb O instead of invaginating as it does during phagocytosis, it forms little balloons that are pinched off from the cell surface membrane O the blebs (vesicles) are phagocytosed

5

How is apoptosis controlled? O Apoptosis is controlled by a number of different cell signals. Some from inside, some outside the cell. O Cytokines (immune system T helper cells) O Hormones O Growth factors O Nitric oxide: makes inner mitochondrial membrane more permeable to H+ and so affecting proton gradient. Proteins released into cytosol which bind to apoptosis inhibitor proteins and so allow apoptosis to take place.

Apoptosis and Development O Important in plant and animal development of tissues O Pruning of cells O Regulated: different tissues=different signals If rate is not controlled O Not enough=tumours O Too much= cell loss and degeneration (old age/degenerative diseases!)

The life cycle of an amphibian involves metamorphosis, with reabsorption of the gills and tail. Apoptosis is responsible for this. Consider the changes that take place in the metamorphosis of amphibian: the larva (tadpoles) are aquatic, have external gills and a tail the adults have lungs, legs and no tail the gills and tail are reabsorbed due to apoptosis Life cycle of amphibian.

O Similarly, during limb development in humans, the tissues have to be rearranged. O Apoptosis allows for the separation of the digits (fingers and toes). O Failure of this leads to syndactyly, i.e. fused digits (toes in the case of the illustration opposite). Failure of apoptosis leads to syndactyly or fused digits, as seen here on the foot.

10 Hand of newborn infant showing complete syndactyly of two fingers.

Check understanding O Outline how apoptosis (programmed cell death PCD) can act as a mechanism to change body plans. O Review the LO O Exam question 6 marks =6 minutes