Introduction To Development
Development, in this journey from a single cell to a complex multicellular organism. Development does not end at birth, but continues with childhood and puberty to early adulthood.
We must describe how a cell from the father and a cell from the mother combine to form a new genetic individual, and how this new cell forms others, how they become organised to form new shapes, specialised interlinked structures, and grow. With this knowledge we become able to understand how these processes can be interfered with, and how abnormalities arise.
Growth may be described as the process of increasing in physical size, or as development from a lower or simpler form to a higher or more complex form.
In embryology, growth with respect to a change in size may crease in cell number, an increase in cell size or an increase in extracellular material (Figure 3.1).
Increasing cell number occurs by cells dividing to produce daughter cells by proliferation. Proliferation is a core mechanism of increasing the size of a tissue or organism, and is also found in adult tissues in repair or where there is an expected continual loss of cells such as in the skin or gastrointestinal tract. Stem cells are particularly good at proliferating.
An increase in cell size occurs by hypertrophy. In adults, muscle cells respond to weight training by hypertrophy, and this is one way in which muscles become larger. During development, hyper- trophy of cartilage cells during endochondral ossification is an important part of the growth of long bones. Be aware that the term hypertrophy can also be used to describe a structure that is larger than normal.
Cells may surround themselves with an extracellular matrix, particularly in connective tissues such as bone and cartilage. By accretion these cells increase the size of the tissue by increasing the amount of extracellular matrix, either as part of development or in response to mechanical loading.
Cells may also die by programmed cell death, or apoptosis. This might be considered an opposite to growth, and in development is an important method of forming certain structures like the fin- gers and toes.
During development, cells become specialised as they move from a multipotent stem cell type towards a cell type with a particular task, such as a muscle cell, a bone cell, a neuron or an epithelial cell. When the cell becomes more specialised it is considered to have differentiated into a mature cell type. If that cell divides, its daugh- ter cells will also be of that mature cell type.
In humans, a mature cell is unlikely to dedifferentiate back into a stem cell, but the process by which this can occur is being exploited in the laboratory with the aim of producing stem cells from adult tissues. These stem cells could then be pushed to dif- ferentiate into the cell type needed to grow new tissue or treat a disease.
A signal from one group of cells influences the development of another (adjacent, nearby or distant) group of cells. Hormones act as signals, for example. For a cell to be affected by a signal it must possess an appropriate receptor.
In the embryo the signalling of a vast array of different proteins by different groups of cells allows those cells to gain information about their current and future tasks, be that migration, proliferation, differentiation or something else.
Early in development the ball of cells or simple sheets of the embryo do not give much clue about which cells will form which structures. It is difficult to determine which part will become the head and which will become the tail. However, the cells are aware of their position and the roles that they will have and we can see this by looking at the signalling proteins and connections between cells.
For example, the upper limb begins to develop as a simple bud of cells. The cells in that bud must be organised to produce the structures of the arm, the forearm and the hand. The ulna bone must form in the right place relative to the radius, and the thumb must form appropriately in relation to the fingers. This may occur partly because a group of cells on the caudal aspect of the limb bud produces a morphogen that diffuses across the early limb bud (Figure 3.2). Cells near the site of morphogen production experi- ence a high concentration, and cells further away on the cranial side of the bud experience a lower concentration. Development of these cells progresses differently as a result. If experimentally you trans- plant some of the morphogen‐producing cells to the cranial part of the limb bud, duplicate digital structures form. See Chapter 25 for more about limb development.
This is one example of how cells organise themselves and others during development. With organisation, structure follows.
The formation of shape during development is morphogenesis.
Cells are able to change the ways in which they adhere to one another, they can extend processes and pull themselves along, migrating to new locations, and they can change their own shapes. In a tissue there may be a change in cell number, cell size or accretion of extracellular material. In these ways a tissue gains and changes shape.
An early example of morphogenesis in embryonic develop- ment occurs with the change from simple flat sheets of cells to the rolled up tubes of the embryo and gastrointestinal tract (Figure 3.3). A simple structure has become more complex. Chapter 14 covers this in more detail.
Interruptions of signalling, proliferation, differentiation, migration, and so on, cause congenital abnormalities. Teratogens that affect development during key periods may have significant effects. For example, if the drug thalidomide is taken during early limb development it can cause phocomelia (hands and feet attached to abnormally shortened limbs). Other environmental factors and genetic mutations can cause abnormal development. The embryo is most sensitive during weeks 3–8.
Dysmorphogenesis is a term used for the abnormal development of body structures. It may occur because of malformation or deformation. If the processes required to normally form a structure fail to occur the result is a malformation. If the neural tube fails to close, for example, the resulting neural tube defect is a malformation. A deformation occurs if external mechanical forces affect development. For example, damage to the amniotic sac can cause nds that may wrap around developing limbs and cause mputation of limbs or digits.