It is remarkable that the fertilized egg of a human, mouse or fish look so similar and are all around a 1mm wide, yet the adult forms of each of these organisms are wildly different in size and appearance. Developmental biology is the study of the processes that transform a fertilised egg into an adult organism.
When an egg is fertilized it consists of a single cell with a complete genome (half comes from the father and half from the mother). The genome contains within it some instructions that will tell the single cell how to grow and divide to make more cells. But then the new cells also need additional instructions from the genome that will tell them what tissues they will eventually develop into. They don’t all want to be the same – if they were we would be a sticky blob of cells with no eyes, ears or anything – which would be extremely inconvenient, to say the least.
Some cells need to be told to become one thing and some need to be told to become something else. Understanding which of these genetic instructions are selected for particular cells, and how they are interpreted by them (bearing in mind that all cells carry a complete set of the same instructions from the very beginning) is the basis of developmental genetics.
Embryogenesis and Differentiation
The development of an embryo from a fertilised egg is called embryogenesis. After fertilisation the egg undergoes a series of rapid divisions to form many identical daughter cells – a process called cleavage. This forms a ball of cells; in fish, this sits on top of the yolk.
After the first few cleavages the cells start to differentiate, which means what it sounds like – they become different from each other.
Some will be destined to form part of the organism’s lungs perhaps, or muscle, others will be neurons in the brain. Although they don’t get segregated into these particular fates at this point, first they become one of three types of tissue (which means more new words to learn!):
- Ectoderm (outer) – mostly forms the skin and nervous system.
- Mesoderm (middle) – becomes muscle, bone and the circulatory and reproductive systems.
- Endoderm (inner) – develops into the respiratory tract (lungs, throat, thrachea, and sinuses), gut and gastrointestinal organs (ie liver, pancreas, gall bladder).
These three types of tissue are called germ layers (some lower organisms only have two germ layers – the ectoderm and endoderm).
Cells migrate into the embryo to form the germ layers in a process called gastrulation. In zebrafish, the cells migrate inwards by the spreading of one sheet of cells over another, during a process called epiboly.
Somitogenesis is the process by which the segmented somites of the embryonic trunk are produced. These tissue blocks differentiate into the skeletal muscle, vertebrae, and skin. In zebrafish the somites are clearly visible, initially as rounded structures along the trunk, which soon become V–shaped. The V–shaped somites can be seen in any adult fish.
Organogenesis is another differentiation stage that forms the organs such as the gut, liver, pancreas and lungs. In the fish the internal organs are visible in the young developing larva – muscle contractions can be seen passing along the length of the gut – as can the passage of food, which of course becomes faeces by the time it reaches the end of the gut tube.
In biology an organism’s shape is called its morphology. Morphogenesis is the biological process that causes an organism to develop its shape. It is Greek and literally means “beginning of the shape”.
Morphogenesis happens because of changes in cell behaviour that affect how cells interact with each other in tissues.
During gastrulation, the DNA recipe is copied into a RNA message (this is called transcription) and then the recipe followed (called translation) to make a particular protein.
A great many different kinds of proteins are needed to make a cell function and to build a whole animal. Three of the most important functional classes of proteins that are able to drive morphogenesis are:
- Transcription factors – proteins that actually read the genome. They transcribe the DNA into an RNA message that can be understood by the cell, and be used as a blueprint to make a protein. Transcription factors look for important information in the DNA that is normally found around a gene. This information helps the transcription factor determine when a gene needs to be read and made into protein.
- Cell adhesion molecules – these are proteins that are found on the surface of cells, which help cells stick together. Cells that have the same kind and quantity of adhesion molecule on their surface will stick to each other, and repel those of a different kind. When this occurs we call it cell sorting – cells that are like each other sort themselves out so that they are in contact with each other. Cell sorting can help arrange the tissues in a developing organism by keeping like with like.
- Morphogens – are messages that are secreted by a cell or group of cells into the surrounding area. Cells in the locality receive these instructions and act accordingly depending on the concentration of message protein they detect. Hedgehog proteins are a very important class of morphogens. To read more about them please see our Hedgehog page.
Development and Disease
Understanding how a healthy organism develops is certainly interesting, but more than that it is crucial to establishing what happens when things go wrong. Embryos with a mutation in a key developmental gene (such as a morphogen or transcription factor gene) will not form properly and will probably not survive. By studying what organs and tissues are affected by mutations in particular genes we can learn what roles they play in normal development and also in congenital diseases that cause birth defects.
Many other diseases – e.g. cancer, CNS (Central Nervous System) disorders are caused by genes with important roles in embryonic development. Development is relevant for understanding more than congenital abnormalities.
Sometimes environmental factors, such as chemicals, can interfere with a protein’s function and cause birth defects. Again, by understanding the role each protein plays during normal development, and how chemicals or drugs affect them, we can hopefully learn how to prevent or treat the effects of enviromental influences on development.
The fundamental aim of developmental genetics is to understand when, why and how different genes are able to form an adult organism from a fertlised egg.