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The third (labeled CP for posterior centrale, BA 3,1,2, primary somatosensory cortex) and fourth (labeled CA for anterior centrale, BA 4, primary motor cortex) areas of the cerebral cortex to myelinate – nissl stain parasaggital section of a 7-month-old human fetus (Flechsig 1921)

Myelinogenesis is the process of sequential myelination or development of myelin sheaths around nerve fibres of the central nervous system.


The myelination process allows brain signals (neural signals) to propagate faster and with less signal loss. This enables better tissue connectivity within specific brain regions and also improves broader neural pathways connecting spatially separate regions required for many sensory, cognitive, and motor functions.

Some scientists consider myelination to be a key human evolutionary advantage, enabling faster processing speeds and leading to further brain specialization. Myelination is considered to be a key developmental stage in the human brain, continuing for at least another 10 to 12 years after birth "before even a general development is completed".[1] Therefore, the rate of development of these brain structures will determine the rate of development of related brain functions.

While the rate at which individual children develop varies, the sequence of development is the same for all children (with a range of ages for specific developmental tasks to take place).


Paul Flechsig spent most of his career studying and publishing the details of the process in the cerebral cortex of humans. This takes place mostly between two months before and after birth. He identified 45 separate cortical areas and, in fact, mapped the cerebral cortex by the myelination pattern. The first cortical region to myelinate is in the motor cortex (part of Brodmann's area 4), the second is the olfactory cortex and the third is part of the somatosensory cortex (BA 3,1,2).

The last areas to myelinate are the anterior cingulate cortex (F#43), the inferior temporal cortex (F#44) and the dorsolateral prefrontal cortex (F#45).

In the cerebral convolutions, as in all other parts of the central nervous system, the nerve-fibres do not develop everywhere simultaneously, but step by step in a definite succession, this order of events being particularly maintained in regard to the appearance of the medullary substance. In the convolutions of the cerebrum the investment with medullary substance (myelinisation) has already begun in some places three months before the maturity of the foetus, whilst in other places numerous fibres are devoid of medullary substance even three months after birth. The order of succession in the convolutions is governed by a law identical with the law which I have shown holds good for the spinal cord, the medulla oblongata, and the mesocephalon, and which may be stated somewhat in this way- that, speaking approximately, equally important nerve-fibres are developed simultaneously, but those of dissimilar importance are developed one after another in a succession defined by an imperative law (Fundamental Law of Myelogenesis). The formation of medullary substance is almost completed in certain convolutions at a time when in some it is not even begun and in others has made only slight progress.[2]


Although the mechanisms and processes of myelination are yet to be fully understood, especially complex gene function, some specific stages in this process have become clear:

  • Stage 1: Axon contact
  • Stage 2: Glial cell gene production
  • Stage 3: Axon ensheathment
  • Stage 4: Maturation.

Many key questions about the myelination process still remain:

  • Why axons of similar size seem to myelinate at the same time;
  • Whether proteins, molecules and genes are involved in determining axon size;
  • If axonal activity influences the process, if there is a causal relationship, or if there is a more complex combined effect;
  • Why certain processes seem to be lost if myelination does not occur.


  1. Myelination in Development
  2. Flechsig, Paul (1901-10-19). Developmental (myelogenetic) localisation of the cerebral cortex in the human subject. The Lancet.


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