I - Neurogenesis

1) Establishment of Neural Networks

The stem cells of the nervous system originate from the dorsal ectoderm. Four major stages allow for the formation of the cells of the nervous system:

• Cell Proliferation: the stem cells of the nervous system (neuroblasts and glial cells) multiply by mitosis in the ventricular zone;
• Cell Migration (genetically programmed, time/space): occurs from the ventricular zone to the marginal zone thanks to guiding glial cells (distribution of migrating cells);
• Differentiation: axonal growth and synaptogenesis. During migration, neural stem cells differentiate into precursor cells of glial cells and into neuroblasts which then differentiate into neurons;
• Axonal Growth: a growth cone forms at the surface of the neuroblast allowing for the formation of the axon. This cone progresses towards target cells secreting an attractive product: NGF (nerve growth factor);
• Synaptogenesis: when the target is reached, synapses form, creating neural networks.

Development of Dendritic Arborization: After synaptogenesis, there are a large number of connections, but some neurons cover identical (redundant) territories; this is the transient redundancy. Two mechanisms will remedy this:

• Cell Death (apoptosis): only the most efficient synapses are preserved (the most active neuron);
• Synaptic Reorganization: the least functional synapses disappear.

2) Epigenesis and Sensitive/Critical Period

There is first a genetically programmed phase of development of the nervous system. Then the environment will influence the development of the structures and functions of the nervous system: epigenesis. Nerve connections stabilize or regress according to the individual’s interactions with the environment: “Learning means eliminating possibilities.”

II - Organogenesis

1) Embryonic Development (forming the organic templates)

Day 0: Fertilization

Day 6: Implantation

Day 15-20: Gastrulation:

• the embryonic disk elongates and takes on a 3D shape;
• formation of the primitive streak: a row of cells forms a groove in the embryonic disk defining the plane of symmetry for the future fetus.

Day 18-22: Neurulation:

• formation of the neural tube and the nervous system from the dorsal region of the ectoderm;
• the neural tube gives rise to the entire central nervous system of the organism;
• cells from the dorsal part of this tube will become the neural crests, which give rise to the PNS;
• the neural tube has different central cavities filled with cerebrospinal fluid. These cavities will become, in adulthood, the future ventricles and aqueduct of Sylvius in the brain and the ependymal canal in the spinal cord;
• the central cavities of the neural tube = future ventricle = aqueduct of Sylvius + ependymal canal;
• the walls of the neural tube contain the nerve cells that develop around these various cavities.

Day 25 (third week): the neural tube differentiates into two parts:

• caudal part: future spinal cord;
• cephalic part: future brain (stage of the 3 primary vesicles: mesencephalon, prosencephalon, rhombencephalon).

2) Development and Organization

6th/7th weeks: Stage of the 5 secondary vesicles:

• Prosencephalon becomes the telencephalon and diencephalon;
• Mesencephalon does not change: stuck above the telencephalon;
• Rhombencephalon: metencephalon (cerebellum) and myelencephalon (pons and medulla oblongata).

Primary Flexures: cephalic (MES) and cervical (MYEL and SC); secondary flexure is the pontine flexure.

The spinal cord differentiates into a dorsal (sensory) part and a ventral (motor) part.

Growth of the Telencephalon: the brain originating from the telencephalon and diencephalon:

• flexures adapt to the shape of the skull;
• Telencephalization of the human nervous system;
• Gyrification: folding of nervous tissue.

Growth of the Cerebral Hemispheres:

• front: frontal lobe;
• back: parietal and occipital;
• back, front: temporal;
• insula: buried under 2 lobes.

Gyrification (6-7 months): cortex folds to maximize surface area without taking up too much volume. Formation of gyri.

3) Myelination and Maturation (Myelogenesis) of the Nervous System

First, in the PNS, motor functions are myelinated first then sensory functions. Then in the CNS, myelination follows for sensory functions followed by motor functions.

• Spinal Cord is highly myelinated, and brainstem is myelinated in the fetus (7 months).
• Maturation of the brain occurs later on.
• Cerebellum: myelination continues until one year and beyond.
• Brain: last areas to be myelinated are in the prefrontal cortex: long-term decision-making centers (associative areas, throughout life but especially during adolescence, around 15-20 years).