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How the mind develops
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From Embryo to Ethics

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Help Link : Neuronal Proliferation and Migration Link : Neural Development Link : The Genetic Basis of Development
Link : Differential gene expression and development Link : Determination and Differentiation Link : Nuclei of dividing cells Link : Differentiation and Diversification
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Tool Module: Apoptosis (Programmed Cell Death) Apoptosis (Programmed Cell Death)

Mitosis is the type of cell division that takes place in human body cells not only during development but also during tissue renewal in adults. A cell that undergoes mitosis passes through several stages that result in its division into two daughter cells that resemble this mother cell. The daughter cells may then divide in turn, which leads to the exponential growth in the number of cells during embryonic development.

Meiosis is the other main type of cell division. It occurs only in gametes (ova and spermatozoa). Meiosis is specific to eukaryotic cells and occurs when a diploid mother cell produces four haploid daughter cells, each of which has a different genome.

When fertilization occurs, a male haploid cell fuses with a female haploid cell to create a new diploid cell.

Link : la division cellulaire Link : La mitose Link : La méiose Link : Méïose... mitose
Link : La mitose et le cycle cellulaire

When a stem cell divides, it can produce two new stem cells, or two neuroblasts, or one stem cell and one neuroblast.

In the first case, the two daughter stem cells will retain the property of producing other pluripotent stem cells.

When a stem cell divides and at least one of its two daughter cells is a neuroblast, differentiation is said to have occurred. A differentiated cell is more specialized in form and function than its mother cell. The differentiated cell can produce only cells of its own particular lineage and cannot go backward and produce stem cells.


The general process that leads to the birth of new neurons is called neurogenesis. Most of the neurons in the human neocortex are formed between the fifth week and the fifth month of gestation.

Though most of the cortex’s neuronal development occurs before birth, certain parts of the adult human brain retain their ability to produce new neurons (follow the History Module link below).

The process of neurogenesis in the adult brain is too limited to replace any populations of neurons that might be destroyed by injury or illness. But researchers hope that by learning learn more about the processes that regulate this neurogenesis, and in particular about the role of environmental factors such as stress, they may begin to devise ways of preserving this ability to grow new neurons, as a treatment for degeneration due to pathology.

History : La naissance de nouveaux neurones dans le cerveau

HOW STEM CELLS FORM NEURONS
HOW NEURONS CONNECT TO ONE ANOTHER

In the space of just a few months, all of a human being’s 100 billion neurons (with a very few exceptions) and an even greater number of glial cells are produced from a small population of precursor cells.

In fact, as soon as the neural tube begins to transform into an encephalon and a rudimentary spinal cord, the production and differentiation of the neurons and the glial cells begins.

The stems cells that proliferate in the ventricular zone of the neural tube are the source of two major families of cells in the nervous system: the neurons and the glial cells. But the cell differentiation does not stop there. The various structures of the brain are formed of countless types of nerve cells that are distinguished by their neurotransmitters, the molecules on the surface of their membranes, the types of synapses that they form, and other such characteristics.

To generate all of this diversity, the processes of cell proliferation, determination, and differentiation must proceed in stages. At each stage, the ultimate destiny of a cell is further defined. More specifically, this maturation occurs through major changes in the replication and expression of genes in the nuclei of these cells.

During the proliferation phase, for example, the cells divide according to the usual cycle of mitosis (see sidebar), but the cell divisions are accompanied by rather distinctive oscillating movements of the cell nuclei. These nuclei go back and forth between the ventricular zone of the neural tube (the part closer to its central canal, or ventricle) and the marginal zone (the part closer to its outer surface).

In phase G1, the growth phase, the newly divided cell begins by extending a narrow cylinder of cytoplasm to the outer surface of the neural tube, at the pia mater. The nucleus and the cytoplasm surrounding it then move through this cylinder toward the outer surface.

In phase S, the DNA-synthesis phase, the nucleus approaches the outer surface and starts to replicate its DNA. Next comes phase G2, the mitosis-preparation phase, in which the nucleus migrates back toward the central canal of the neural tube while the cell continues to develop. The cell then retracts its extension to the outer surface and enters mitosis (phase M).

Based on material from Crump Institute for Biological Imaging

Each cell division gives rise either to more new stem cells or to cells called neuroblasts that will differentiate into neurons (see sidebar). The new stem cells will continue the mitotic division cycle by sending out their own extensions to the outer surface of the neural tube. But the neuroblasts will leave the ventricular zone and migrate to their final locations in the developing brain.

One possible explanation for this strange back-and-forth movement might be that the nucleus needs to be exposed, in a particular time sequence, to various cytoplasmic factors located in various areas inside the cell. This phase of intense cell proliferation results in an excess production of neurons, whose numbers will then be reduced by apoptosis (for more on apoptosis, follow the Tool Module link at the top of the left-hand column).

 

 

After their last mitosis in the ventricular zone, most of the newly formed neuroblasts begin a migration that will take them to their final position. Neuroblasts guide themselves in various ways in the course of their migration. In certain parts of the brain, such as the cortex and the cerebellum, the migration of a large portion of these cells is facilitated by radial glial cells that send out extensions from the ventricular zone to the cortical surface.


The structure, function, and activity of a cell depend in large part on its genes. The sequence of cellular events that leads to the differentiation of the neurons is thus controlled partly by intrinsic factors—in other words, by cellular mechanisms that activate and deactivate genes. For example, retinoic acid, a derivative of vitamin A, activates specific receptors that modulate the expression of certain genes.

But in eukaryotic cells, the expression of the genes (or phenotype) is always influenced as well by extrinsic factors (also called epigenetic factors) from the cell’s environment.

Transplant experiments have thus shown that if the grafted cells are taken from an animal whose development is fairly advanced, these cells will retain their original phenotype as they develop in their new host. But the younger the animal from which the grafted cells come, the more likely these cells will be to adopt their host’s phenotype as they develop. This indicates the important influence of the extracellular factors in the new environment.

To understand the development of the nervous system, we must thus constantly examine how the intrinsic and extrinsic signals combine to ensure that the processes of determination and differentiation take place successfully.

Link : Une nouvelle génération de neurones … à partir de cellules souches embryonnaires Tool : Les gènes homéotiques


       

Linked
Link : Synapse Formation and Modification

Some nerve cells, such as motor neurons, wait until they have arrived at their final locations before sending out their axonal and dendritic extensions. Other nerve cells, such as the granular cells in the cerebellum, develop their extensions while they are still migrating (see boxed text at the bottom of this page).

HOW NEURONS CONNECT TO ONE ANOTHER
HOW STEM CELLS FORM NEURONS

The location of each neuron in the human brain is more critical than the locations of the others cells in the human body, because neural functions depend on precise connections between neurons and their targets. In other words, the presynaptic and postsynaptic components must be in the right place at the right time.

After the proliferation phase, the neuron precursor cells leave the ventricular zone of the neural tube and migrate to their final locations in the brain. Once each neuron reaches its final destination, its cell body develops the axon and dendrites that will enable it to make connections with other neurons.

To make their connections, the axons must find their specific target cells, which is no small task. The process of forming an axonal pathway can be divided into three phases: selecting the right route, choosing the right target, and finally establishing a connection at the right destination.

For example, consider the case of an axon from a ganglion cell in the retina that must reach the lateral geniculate nucleus in the thalamus. Initially, this axon follows the optic nerve, but very soon, it reaches the optic chiasm, where it must choose one of three routes: the left optic tract, the right optic tract, or the contralateral optic nerve. Depending on whether this ganglion cell comes from the nasal side or the temporal side of the retina, it must select the correct route: either the contralateral optic tract or the ipsilateral optic tract.

Even once it reaches the thalamus, the axon’s work is not over. It still has a choice of a good dozen possible targets. But it has to choose the right target on the thalamus: in this case, the lateral geniculate nucleus (LGN) and not the medial geniculate nucleus or the pulvinar.

Lastly, the axon must establish itself at the correct final destination of its journey—in this case, the correct layer of the lateral geniculate nucleus and the proper retinotopic position.

 

Once it reaches its target, the axon develops a multitude of synapses with it. A selection process that depends on the activity of the neurons will then reduce the number of these synapses so that only those that play a significant role in the neural circuits are retained.


Source: Dr. Brian E. Staveley, Department of Biology, Memorial University of Newfoundland

Long after birth, this mechanism of synaptic reinforcement associated with neuronal activity continues to influence our synapses so as to adjust our bodies to our activities and to our perceptions of the outside world.

It is the circuits laid down during these processes that are the source of our vast repertoire of behaviours. But the development of the nervous system does not stop at birth. After birth, the experiences that each of us has continue to shape our neural circuits.

Some of the mechanisms employed in the early stages of embryonic development will even adjust so that they continue to contribute to the modifications that the brain undergoes throughout life. This plasticity, which enables us to adapt to the changing conditions in our environment, is regarded as the basis of human memory.

The first neurons to be formed in the ventricular zone of the cerebellar cortex are the Purkinje cells and the Golgi cells, which migrate to the marginal zone immediately. The ventricular zone also produces precursor neurons that migrate beyond the Purkinje cell layer to form a second germinal zone called the outer granular layer. It is from this layer that the three main kinds of interneurons in the cerebellum will develop: basket cells, stellate cells, and granular cells. The birth of these interneurons coincides with the elongation of the dendrites of the Purkinje cells.

To reach their final destination, the granular cells must migrate first through the molecular layer and then through the Purkinje cell layer. Upon arriving in the molecular layer, the granular cells develop two extensions parallel to the surface of the cerebellar cortex and perpendicular to the dendrites of the Purkinje cells that are in the process of developing. A third extension soon forms and descends to the granular layer. The body of the granular cell then simply has to follow this extension to reach its final position in the granular layer, leaving behind the two extensions that form the parallel fibres which make connections to the dendrite branches of the Purkinje cells.


Differentiation of granular cells and Purkinje cells in the cerebellum

Source: Mineko Kengaku, Laboratory for
Neural Cell Polarity
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