Brain development in humans

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Embryogenesis of the vertebrate brain: the neural tube (not illustrated) first differentiates into prosencephalon , mesencephalon and rhombencephalon (left half of the picture, approx. 4th week). The prosencephalon then differentiates into diencephalon and telencephalon . The diencephalon differentiates further.

The brain development in humans (also: brain development ) begins in the third week of pregnancy and only after puberty , more than 20 years after the birth , largely completed.

Of the primates , humans have the largest brain in relation to their body mass . This enables him to use his typical human abilities, such as a pronounced ability to learn , complex social behavior and communication through language .

The stages of brain development

The development of the human brain can be divided into several stages, which however gradually merge into one another.

Prenatal brain development

From the third week of development , the human embryo begins to develop the brain and nervous system . For this purpose, a tube of nerve tissue, the neural tube, is formed along the spinal cord from the neural plate (a cell plate on the back of the embryo) . In this the emerging nerve cells grow to their destination, orienting themselves on radially aligned glial cells .

In the fourth to sixth week the neurons form into three bulges, the primary vesicles . From these the brain areas forebrain, midbrain and hindbrain are formed. The eye bud sits on the primary vesicle of the forebrain and the ear bud on that of the hindbrain. The two hemispheres of the brain are formed from two bulges in the forebrain . These grow rapidly and begin to spread over the back of the brain. From the eleventh week the cerebellum begins to develop. At birth, the brain then has its full number of nerve cells.

When looking at the development of the nervous system and thus the brain, there are roughly five different stages:

  1. Neural Induction
  2. Neural Proliferation
  3. Migration, Aggregation and Differentiation
  4. Forming the connections
  5. neuronal apoptosis and selection of synaptic connections

Neural Induction

Neuronal induction is about part of the ectoderm (the outer layer of cells in the embryo) turning into tissue that is suitable for the formation of nerve cells, namely the neuroectoderm (the neural plate). In other words, this is the first time that the prerequisites for a nervous system and thus a brain to develop. This process is brought about by a complex chain of effects of various induction molecules:

  • Fundamental for this is the inhibition of the release of BMP (bone morphogenetic protein), which would otherwise prevent neuronal development. This inhibition, in turn, is caused by substances such as follistatin, chordin and noggin, which are formed in the notochord. The notochordal process is a star-shaped structure in the mesoderm (middle cell layer of the early embryo) that fuses with the ectoderm. This is one side of the differentiation of the cells in the ectoderm into neuronal stem cells , which is induced by the mesoderm, i.e. another cell layer.
  • But there is also another effect factor. Recent studies have shown that FGF (fibroblast growth factor) serves to suppress the transcription of BMP at an earlier stage . In addition, FGF is necessary to lead to a neuronal design of the cells. Finally, the neuronal tube itself differentiates, which leads to the formation of the three known brain areas in this order: forebrain, midbrain and hindbrain, as well as the spinal cord. Differentiation is induced by modulating gene expression :
  • First of all, the prechordal plate in the forebrain causes the differentiation of cells through the expression of transcription factors such as Emx (empty spiracle), Lim and Otx (orthodenticle).
  • This task is performed by the cordal process and the paraxial mesoderm on the mid- and hindbrain.
  • Furthermore, the isthmus organizer seems to play an important role in the organization of the brain through the expression of FGF and en (engrailed). In this condition, the cells are not yet particularly specialized and minor tissue damage can easily be compensated for. For example, tissue from the forebrain-eye field can be removed without causing permanent damage, as the loss of cells is simply compensated for by increased cell division .

Neural Proliferation

From around the 23rd day of pregnancy, so-called proliferation occurs , a phase of increased cell division of the neuron stem cells. While the number of cells in the neuronal tube is relatively small at approx. 125,000 cells, as soon as the neuronal tube is closed there is a sudden increase in the rate of division, in which all cells are involved at this stage. The cells migrate in a division cycle from the outer surface of the neuronal tube to the inner surface, to which they are connected by a thin extension. Before they divide, the cells draw in these processes in order to form them again immediately after dividing. Depending on whether the division cycle is symmetrical (i.e. vertical) or asymmetrical (i.e. horizontal), two new cells are created that retain their ability to divide, or one cell with and one without renewed division. After several division cycles, depending on the area of ​​the brain and the cell density there, the cells leave the division cycle and migrate from the ventricular layer to the intermediate layer, where they differentiate into postmitotic neurons. The intermediate layer then ultimately consists of young cells without any ability to divide and precursors of glial cells with a lifelong ability to divide. This process of division and differentiation is known as neurogenesis . It is still unclear how exactly the formation of the various nerve and glial cells is coordinated at the various positions in the nervous system. In principle, however, it seems to take place in the brain in a similar way to the spinal cord: Each nerve precursor cell receives positional information from signals produced outside the neural tube. This position in connection with the point in time at which the cell was formed then determines its later fate. The gradient of SHH molecules (sonic hedgehog molecules) is primarily decisive for the later region. Depending on its concentration, the control of homeodomain class I transcription factors, which are suppressed, and class II factors, which are induced, is lost in the neuron progenitor cells. SHH thus leads to the formation of five different strips of ventral progenitor cells. These patterns later determine which transcription factors are expressed in the neuronal cells.

The time of leaving the cycle of division also seems to play a role in later differentiation. Three statements can be made:

  1. Large neurons, or those with relatively long axons, are generally created earlier than small neurons, or those with relatively short axons.
  2. The pattern of the times at which the cells leave the division cycle differs depending on the brain region. For example, cells in the cerebral cortex that are closer to the surface later stop dividing. In the retina of the eye, on the other hand, it is exactly the opposite: here cells that come to rest in the more superficial layers of the retina hear to divide earlier.
  3. Although the first glial cells develop together with the first nerve cells, their production outlasts that of the nerve cells.

Migration, Aggregation and Differentiation

The migration of the cells afterwards is amoeboid, that is, the cells send out an extension along which they “flow”. In doing so, they are guided by special glial cells that have formed processes from the ventricular layer to the neuronal tube. The average migration speed is about a tenth of a millimeter per day. Occasionally cells also miss their destination and end up in the wrong positions. However, these can be eliminated later. As soon as the nerve cells have reached their final position, they begin to form aggregates - clusters of cells - and thus the various structures of the brain. Molecules on the cell surface probably enable the cells to recognize one another and to attach to one another. In addition, the neurons also have a certain orientation. For example, the alignment of the pyramidal cells is such that their apical dendrites (starting from their tip) are perpendicular to the brain surface, while their axons, on the other hand, run in the direction of the white matter. In addition, in this phase of differentiation, the nerve cells select the conduction and transmission of excitation in the synapses.

Forming the connections

Most neurons in mammalian brains are multipolar, which means that they form numerous tapered dendrites but only a single axon. The formation of these structures takes place when the cell has reached its final position. How the growing nerve fibers manage to find their predetermined path depends on a number of complex mechanisms. There are three questions to be distinguished:

  1. How do the axons find their way? (pathway selection) - Some nerve fibers seem to grow together along a chemical gradient. Others, in turn, may orientate themselves towards their neighbors.
  2. How do you recognize the target area? (target selection) - The correct target area is likely genetically predefined.
  3. How do you recognize the target cell? (address selection) - Above all, activity-dependent processes play a major role here. Closely related to this are the molecular and cellular processes of learning in organisms.

Once the target cell has been identified, synapses are formed between the nerve cells. The NGF (Nerve Growth Factor) is decisive here; without it, a functioning nervous system cannot develop. The point in time when synaptogenesis (formation of the synapses) takes place differs from brain region to brain region. Sometimes it even lasts beyond pregnancy. In the prefrontal cortex, for example, it lasts until adolescence.

Neural apoptosis and selection of synaptic connections

At about the same time as the process of synaptogenesis, apoptosis occurs, that is, the controlled death of cells. Since a large number of cells were formed in the early stage of development of the nervous system, apoptosis of up to 85% of the neurons occurs, depending on the brain region. This happens because all nerve cells compete for synaptic contacts. Neurons that are not able to form a certain number of interconnections die as a result. This has two goals at once: on the one hand, the quantitative compensation of interconnected neuron populations and, on the other hand, the resolution of failed, incorrect connections. The number of surviving nerve cells is therefore dependent on the required synaptic contacts that result from the target area of ​​the nerve association. For example, more motor neurons remain in the spinal cord when an additional extremity is implanted in the embryo. The triggering factors for apoptosis can be:

  1. Apoptogenic membrane receptors are activated, especially by TNF-α or cell death-specific ligands such as FAS
  2. nucleus-bound receptors are activated
  3. various stress factors have an impact
  4. and the most important trigger is the lack of “survival signals” - growth-inducing molecules such as NGF, BDNF, CNTF

A little later, the number of synapses also adapts. For example, in adult mammals, the individual muscle cells in the extremities are innervated by just a single synapse. In development, however, there is a phase of multiple innervation. During the second and third weeks after the birth, all the surplus synapses disappear except for one per muscle cell. Here, too, there is a kind of adaptation to the given circumstances, which is controlled depending on the activity. The activity can either originate from the cell itself (endogenous activity) or from signals arriving from outside (functional activity). On average, around 40% of the originally formed synapses degenerate again.

Development of the cerebrum and cerebral cortex

The two halves of the brain develop because they form protuberances on both sides from the lateral wall of the prosencephalus (the primary vesicle of the embryonic brain located furthest “towards the mouth”, consisting of the end brain and the diencephalon), which continue to enlarge. In principle, the perikarya (gray matter) accumulate around the central CSF space during the development of the brain, whereas the axons (white matter) come to rest further outside. However, it comes in the regions of the cerebral hemispheres and cerebellum also to the formation of gray matter at the surface, so-called bark . This happens because neurons that were originally formed in the immediate vicinity of the vesicles migrate to the outer regions of the cerebral hemisphere. Ultimately, a 6-layer and approx. 2 mm thick layer is formed from 10 to 14 billion nerve cells and about ten times as many glial cells. From the 18th week of pregnancy, the cerebral cortex then has its typical shape, which is characterized by fissures (crevices), sulci (furrows) and gyri (convolutions). Neurons inside, on the other hand, form what are known as the basal ganglia .

Development of the cerebellum

In the cerebellum, too, gray matter is found both inside as the core area and on the surface as a tripartite cortex . The histogenesis (development) of the cerebellum takes place from the fifth week and is based on two different zones:

  • Inner germ layer of the wing plates of the metencephalon: This is where those cells are formed that migrate from the 6th to the 8th week and thereby form the core areas. Furthermore, from the ninth week onwards, neuroblasts for the Purkinje cells, which also migrate, and finally the stellate cells, basket cells and Golgi cells.
  • rostral part of the rhombus lips: it represents the place of formation for the granular cells, which migrate to the cerebellar surface from the 11th week and form the outer granular layer. The development of the cerebellum is far from over. The formation of the neural network of the Purkinje cells and the migration of the neurons of the outer granular layer continues for a few years after birth.

During the entire pregnancy, the neural network is extremely fragile and therefore susceptible to any environmental influences that could harm it. So z. B. Alcohol lead to fetal alcohol syndrome, which can be associated with considerable damage.

Postnatal brain development

Even if all nerve cells are already present at birth, the development of the brain is far from complete. A functioning network has yet to develop; At the time of birth, a rough framework is only in place. This is why the brain and nerve network grow extremely rapidly up to the age of six, after which development slows down until it is finally completed beyond the age of 20.

Myelination

If nerve cells are myelinated, a coat of oligodrendroglial cells forms around them, which leads to a considerably improved conductivity and is therefore necessary to form meaningful, intact connections in the brain. It begins in the second trimester of pregnancy, but reaches its peak within the first eight months of life. Ultimately, this - in combination with the selection of connections - leads to the speed of the nerve impulses increasing by a factor of 16. During myelination, the following rules can be determined for the order in which the axons are encased:

  1. Proximals are myelinated before distal connections
  2. Sensory neurons come before motor ones
  3. First specific afferents coming from the thalamus, then the non-specific ones
  4. The central ones are myelinated in front of the polar areas of the cerebrum
  5. occipital are myelinated in front of temporal poles

The growth in size of the brain can also be explained by the sheathing of the nerve fibers with the myelin sheath - because the number of neurons themselves does not increase.

Synaptogenesis and selection of synapses

The process of synaptogenesis is also far from complete at birth, with an average of 2,500 synapses per neuron. In small children, this number is already 15,000, the brain of a 2-year-old already contains as many synapses as that of an adult and that of a 3-year-old even twice as many. They are then broken down again up to the age of ten. This enormous number of connections per nerve cell suggests a very high adaptive and learning ability at the age of two to ten years. In addition, the majority of selection processes of neural connections take place in the period after birth. In combination with the points above, this indicates that the development of the brain is largely determined by its environment and that only the basis of this development is genetically determined prenatally. The adult brain can then only be changed and rebuilt to a limited extent.

Development of thinking and remembering processes

The ability to form memories is already invested in the toddler, but the period for which a memory can be stored is initially quite short. He is

  • for 6 months: 24 hours
  • for 9 months: 1 month

and continues to increase over time. Because of this, events from 3/4 are generally not remembered. Year of life and only very weakly from the 5/6. From around the age of four, communication between the right and left hemispheres of the brain is significantly improved, which enables logical, analytical thinking. Studies with the MRI have also shown that the proportion of gray matter and white matter in the brain shifts in favor of white matter from around 12 years until adulthood.

Developmental disorders

Depending on the stage of brain development, harmful external influences can damage the brain and impair its development. Genetic, toxic and infectious influences are in the foreground in the first and second trimester of pregnancy, while hypoxic-ischemic, infectious or thromboembolic events in the latter.

literature

  • Tony Smith: Anatomie-Atlas , DK-Verlag, Munich, 2007, ISBN 978-3-8310-1116-2 Title of the English-language original edition: Human Body , DK-Verlag, London, 2002.
  • Renate Huch, Klaus D. Jürgens (eds.): Mensch - Körper - Disease , Urban & Fischer Verlag, 6th edition, Munich, 2011, ISBN 978-3-437-26792-5 .
  • Olav Wieser et al .: Anatomie , Neuer Kaiser Verlag, Klagenfurt, 2006, ISBN 978-3-7043-6057-1 Title of the original Italian edition: Atlante de Anatomia , Giunto Gruppo Editorale, Firenze, 2000.
  • Ralf Burger, et al .: Natura 12 - Biology for High Schools , Ernst Klett Verlag, 1st edition, Stuttgart, 2010, ISBN 978-3-12-045570-7 .
  • Fred T. Adams: Der Weg zum Homo sapiens , Suhrkamp Verlag, Frankfurt am Main, 1971 Title of the English-language original edition: The Way to Modern Man , Teachers College, Columbia University, New York, 1968.
  • W. Maxwell Cowan: Development of the Brain , In: Spectrum of Science: Understandable Research: Brain and Nervous System , 9th Edition, Heidelberg, 1988, ISBN 3-922508-21-9 .
  • William H. Calvin: The Symphony of Thought - How Consciousness Arises from Neurons , Carl Hanser Verlag, Vienna, 1993, ISBN 3-446-17279-3 Title of the original English-language edition: The Cerebral Symphony - Seastore Beflections in the Structure of Consciousness , 1989 .

Web links

Individual evidence

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    Interview with Jay Giedd, Professor of Psychiatry, University of California, San Diego.
    Puberty puzzle. Fog behind the forehead. In: spiegel.de. May 4, 2010.
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  5. ↑ a b Dr. Kipp, Cengiz Yavas and Bettina Burgardt: The development of the brain and its risks , lecture at Saarland University, In: Seminar on neuropsychological developmental disorders , 2006.
  6. ↑ Definition of the notochordal process in the medical lexicon of Gesundheit.de (accessed April 20, 2015)
  7. ↑ Definition of mesoderm in the medical lexicon of Gesundheit.de (accessed: April 20, 2015)
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  9. ↑ a b Molecular mechanisms during early embryonic development of the CNS (accessed April 20, 2015)
  10. ↑ Neural Basics (accessed April 20, 2015)
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  13. ↑ Lexicon of Science: Nervenzellwanderung , In: Spectrum - Understandable Research, 2000, Heidelberg.
  14. ^ A b c Karl-Friedrich Fischbach, Heinz Gert de Couet and Markus Hofbauer: Neurogenetics , Chapter 43 in: Prof. Wilhelm Seyffert: Textbook of Genetics, Gustav Fischer Verlag, 1998, oO, ISBN 3-8274-0787-7 . (Accessed April 21, 2015)
  15. ↑ Apoptosis (accessed April 22, 2015)
  16. ↑ Entry on Isocortex in Flexikon , a Wiki of the DocCheck company , accessed on April 19, 2015.
  17. ^ Lexicon of the natural sciences: cerebral cortex , In: Spektrum Akademischer Verlag , Heidelberg, 2000.
  18. ↑ Basics of brain development - histogenesis of the cerebral cortex (accessed April 20, 2015)
  19. ↑ Basics of brain development - histogenesis of the cerebellar cortex (accessed April 20, 2015)
  20. ↑ Bell JC, Raynes-Greenow C, et al. Maternal Alcohol Consumption during Pregnancy and the Risk of Orofacial Clefts in Infants: a Systematic Review and Meta-Analysis . In: Pediatric and Perinatal Epidemiology . 2014 Jul; 28 (4): 322-32. ISSN  1365-3016 . doi: 10.1111 / ppe.12131 . PMID 24800624 .
  21. ↑ Chrysanthy Ikonomidou et al .: Ethanol-Induces Apoptotic Neurodegeneration and Fetal Alcohol Syndrome. In: Science of February 11, 2000. doi: 10.1126 / science.287.5455.1056 .
  22. ↑ Johanna Braig: Neurological foundations of development. Chapter 3 in: Rolf Oerter and Leo Montada (eds.): Developmental Psychology. Beltz PVU, Weinheim 2008.