2 Growth and development: the big picture
The scale of the problem facing the human zygote is vast. The zygote, the single cell resulting from the fusion of a sperm and an ovum, is about the size of a full stop on a nomal printed page, yet within 9 months it has become a 3 kg, 50 cm long baby. The single cell has made millions of other cells; 1011 (i.e. 100 000 000 000) neurons in the brain alone. Not only is there this vast and rapid increase in the number of cells (some calculations put the peak figure at 250 000 new neurons being born every minute!), but there is also the problem of organising the constantly growing population of cells into organs and tissues. For neurons there is the additional problem of making appropriate connections between each other, to effector organs (e.g. muscle) and with sensory organs.
The mechanisms which control and direct the development of the nervous system are, for the most part, beyond the scope of this course. The growth of axons, though, is considered in some detail in Section 6.2. Here, a brief account of what happens as the nervous system develops is given to provide an overview of what must be one of the most remarkable processes on Earth.
The zygote divides in two and those two cells also divide in two. The resulting four cells divide in two, producing eight cells and so on. The process of division continues with very little increase in the size of the sphere of cells until day seven when implantation into the uterus occurs. By embryonic day 15 (E15) the various structures necessary to sustain the embryo are in place. These structures, which include the placenta, amniotic cavity and yolk sac, have all been produced by the embryo through the processes of cell differentiation (the transformation of one cell type into another) and cell migration (the movement of cells from one place to another). At this stage, the embryo itself is a flat germ disc comprising two layers of cells: a layer of endodermal cells with the flattened sphere of the yolk sac to one side and a layer of ectodermal cells with the flattened sphere of the amniotic cavity to the other side (Figure 3a). This thin little germ disc is the ultimate source of all the cells in the human body.
On about day E15, the two layers of cells that comprise the germ disc begin to separate from each other forming a cavity between them. Ectodermal cells flow into the cavity creating a third layer of cells called mesoderm between the endoderm and ectoderm. The movement also creates a groove called the primitive streak along the midline of the germ disc (Figure 3b). This is the first sign of any structure within the embryo itself. The primitive streak defines the central axis of the future human being, where the backbone will form. The three germ layers (ectoderm, mesoderm and endoderm) produce and receive chemical signals causing further changes in structure. The cells that occupy the central axis of the mesoderm exhibit increased adhesion and stick tightly together, separating from their neighbours and producing a rod shaped structure called the notochord, which is the beginning of the backbone. Now the cells on either side of the notochord become adhesive and they stick together, but not enough to cause complete separation from their neighbours. These clumps of cells are somites which will develop into the muscles that lie on either side of the backbone. At the same time as the somites are being formed, the ectodermal cells on top bulge up on either side of the midline, and these neural folds form a neural groove, shown in cross-section in Figure 4.
The upper part of the neural folds come together and fuse along the midline of the embryo producing the neural tube, from which the brain and spinal cord develop (Figure 5).
The cells that form the neural tube will eventually give rise to neurons (they are neural precursor cells). Whilst they retain the ability to divide they are stem cells, but once they stop dividing they are neuroblasts. Those neuroblasts near the notochord will become motor neurons, whilst those further from the notochord will become sensory neurons. The cells just above the neural tube form the neural crest and these cells migrate away from the neural tube to form the neurons and glia of the sensory and sympathetic ganglia, the neurosecretory cells of the adrenal gland and the enteric nervous system, depending on which migratory path the cells take. (See Figure 6.)
The neural tube goes on to form the brain and spinal cord. The tube swells at one end, this will become the forebrain, and there are two smaller swellings behind it, which are the rudiments of the midbrain and hindbrain. At these swellings the hollow core of the tube becomes the ventricles. Within the walls of the tube surrounding the ventricles, stem cells divide to produce neurons and glial cells, which move and adhere to form the characteristic structures of the brain, such as the cerebellum, medulla, etc.; neurons clump together to form distinct structures and axons begin to link them together. At five or six weeks the tube has to bend to accommodate its own growth within the skull. Two bends occur at very specific places and thereby locate the brain in its characteristic position with respect to the spinal cord. From then on there is a rapid appearance of recognisable structures.
The remarkable similarity in the early stages of development between a variety of different vertebrates was first illustrated by Haeckel in 1874. His drawings of embryos are still to be found in many texts (e.g. Figure 7a), but are now regarded as overemphasising the similarlities.
The animation below shows the appearance of vertibrate embryos at three stages of dvelopment. Use the buttons at the top to select the species you wish to view and then use the slider to the left to increase or decrease the development stages.
The similarity is evident both at a structural and a biochemical level. A similarity at the biochemical level between different species is not unusual; a number of other processes, e.g. respiration and neurotransmission share the same biochemical pathways, and the similarity extends beyond vertebrates, to flies and even worms in some cases. The term used to describe the situation where a particular biochemical pathway is the same or has been conserved across species is biochemical parsimony.
Once the human embryo has developed a human body plan, at about E56, it is, by convention, called a fetus, also 56 days old. By the end of the third month after conception, cerebral and cerebellar hemispheres are obvious, and the thalamus, hypothalamus and other nuclei within the brain can be distinguished. In the following month the cerebral hemispheres swell and extend. By the fifth month the characteristic wrinkles of the cerebral hemispheres begin to appear. Most of the sulci and gyri are apparent by the eighth month of development although frontal and temporal lobes are still small by comparison with the adult, and the total surface area is much below its eventual size. The annimation below illustrates the growth of the human brain, use the slider to the left to advance the annimation along the timescale. Note the exceptional growth of the part of the brain which gives rise to the cerebral hemispheres (labelled as the forebrain rudiment at 40 days).
Virtually the full adult complement of neurons in the human brain is present shortly after birth, though the extent to which stem cells continue to produce neurons throughout life is not known. Glial cells continue to increase in number until adolescence, when the mature adult brain structure is achieved. It is largely the increase in glial cell number and the growth of axons, myelin and dendrites that leads the 350 g newborn brain to become the 1300 g adult brain.
There are many developmental paths to maturity and beyond, so you should not think of development as proceeding in an inevitable way along a prescribed path. As the organism grows and develops and acquires a history, so its attributes of size and shape and abilities, its phenotype, serves to distinguish it more and more from all other organisms. And although changes to the phenotype are continuous, they become more subtle as time proceeds: the embryo creates pathways and brain structures, the adult modifies connections and synapses (Figure 1).
The extent to which various environmental factors impact upon development is considered in the next section.