THE BRAIN FROM TOP TO BOTTOM

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From Embryo to Ethics

The precursor cells of neurons proliferate in a part of the neural tube called the ventricular zone, adjacent to the neural tube’s central canal. During the period of maximum proliferation while the embryo is gestating, an estimated 250 000 new neurons form in the ventricular zone every minute!

At a certain point in its development, each stem cell that is destined to produce a neuron divides into one stem cell and one neuronal precursor cell, called a neuroblast. This neuroblast continues to divide while forming various lineages of neurons. At some point in time, the differentiated neuronal precursor cell ceases the cycle of mitotic cell division. This moment marks the birth of the resulting neuron.

Complex structures in the nervous system, such as the spinal cord and the cerebral cortex, contain not just one but many types of neurons. These various types of neurons do not all develop at the same time. Often one type arises from another, forming what are known as cell lineages. One stem cell can thus give rise to various types of neurons (sensory neurons and motor neurons, for example), often using different neurotransmitters.

The term neural stem cells refers to all of the cells that are the source of the various types of neurons found in the brain and even of the various kinds of glial cells in the nervous system. The ultimate fate of the migrating daughter cells therefore does not depend on what kind of stem cell they come from, but rather on a multitude of other factors, such as the age of the precursor cell, its environment, and the orientation of its cleavage plane when it divides.

HOW STEM CELLS FORM NEURONS

How can a single cell, the fertilized ovum (egg), give rise to so many different kinds of cells in the human body, ranging from neurons to blood cells to skin cells?

To begin answering this question in very simple terms, we should first remember that every cell in the human body contains all of the genes capable of forming a human being. The same is true of the cells in a developing human body, especially if you go back to the very start of an embryo’s life. A given cell acquires its specific personality because only certain genes among all those it possesses will be activated—the genes specific to neurons or skin cells, for example.

The next question is: how do all the many different kinds of nerve cells develop, and how do they manage to make their billions of connections correctly in the human brain?

To attempt to answer this difficult question of the origin of our nerve cells, we must look at three processes that act together to transform the precursor cells, known as stem cells, into mature neurons.

The first of these processes is cell proliferation, which increases the number of cells. Since the body needs to manufacture an astronomical number of neurons—100 billion in the adult human brain—it has to start doing so early in the embryo’s development.

Proliferation begins as soon as the closing of the neural tube is completed. At this stage, the neural tube consists of only a single layer of epithelial cells. But as soon as these cells start to proliferate, this layer thickens rapidly (see sidebar).

The next process involved in the origin of our nerve cells is called determination. This is a critical stage in which the destiny of certain cells is decided. They become the precursors that will eventually give rise to various types of neurons and glial cells.

As soon as the major axes of the nervous system have been laid down, the cells in each region can begin to differentiate.

Differentiation is the third process in the maturation of the neurons.

Through differentiation, a given population of neurons gives rise to subpopulations that are specific to the various parts of the nervous system. During this stage, the neurons continue to proliferate and migrate to their final locations, where they will make specific connections with other neurons.

The cerebral cortex is organized into numerous columns that constitute the brain’s basic information-processing units. The expansion of the cortex that has occurred throughout the course of evolution has been attributable to an increase in the number of these columns, not in their individual size.

Because each column originates in a small number of adjacent stem cells, an increase in the number of columns must presumably be due to an increase in the number of stem cells. It is therefore highly likely that some minor changes in the initial quantity of stem cells could be the source of the vast cortical surface found in the brains of primates in general and human beings in particular.

The “Coming Out” of the Electrical Synapse

The dendrites and the axon endings can be perpetually moving and adjusting to one another throughout a person’s life. This phenomenon contributes to the synaptic plasticity that is the basis for learning.

The greatest amount of cell proliferation takes place during the first few weeks of an embryo’s development. After the baby is born, the multiplication of synaptic connections becomes the predominant phenomenon.

The dendrites of neurons are somewhat like the branches of trees: some neurons’ dendrites have only a few branches, while others display extensive, complex branching patterns. Neurons that have only a few dendrites can receive only a limited number of synaptic connections from other neurons, while those neurons that have the most complex networks of dendrites can receive up to 100 000 such connections! By thus determining the number of connections that a neuron can receive, the number of dendrites profoundly influences the neuron’s future function.

HOW NEURONS CONNECT TO ONE ANOTHER

Compared with the development of the body’s other systems, the development of the nervous system poses a special problem. Outside the nervous system, the cells of the human body belong to homogeneous populations. For instance, a beta cell in the pancreas will secrete insulin, no matter where in the pancreas that cell is located.

But the situation for neurons is completely different, because their position in the nervous system determines their function. A cholinergic neuron (one that produces acetylcholine as a neurotransmitter) in a motor area of the spinal cord has a very different function from a cholinergic neuron in the retina or the temporal cortex.

The role that a neuron plays in the brain thus depends not only on the type of neurotransmitter that it secretes or the varieties of receptors that it has, but also, to a great extent, on its location. Why? Because its location largely determines the connections that it will make with other neurons. It is these connections that make our thoughts and behaviours possible.

For one neuron to be able to make connections with others, it must first develop its characteristic extensions: the dendrites and the axon. The nerve cells begin to develop these extensions once they have completed their proliferation and their migration to their final locations in the brain.

The differentiation of these extensions begins when two protrusions called neurites form at diametrically opposite positions on the cell body. One of these protrusions elongates to form the axon, while the other branches to form the dendrites. This differentiation occurs even when neuron-precursor cells are grown in a nutrient medium in the laboratory, which indicates that a portion of this differentiation is genetically programmed.

The axon develops by means of a growth cone at its tip. This growth cone is sensitive to the various chemical signals in its environment and determines the direction of elongation of the axon.