How did brain development evolve to produce the human brain?

How could evolution produce a highly complex, efficient and still-evolving structure such as the human brain? In this article we look at the evolution of the brain across humans as well as other creatures to begin solving this mystery.

Charles Darwin stated, “community in embryonic structure reveals community of descent.” Thus, to understand how the human brain emerged during mammalian evolution we need to understand the evolution of the development of the nervous system that produced our brain and in particular the enlarged cerebral cortex.

The adult mammalian brain contains millions of neurons that are interconnected with billions of connections with trillions of connectivity. Not all brains look the same; see Figure 1 or take a look at the Neuroscience Library.

Figure 1: Brains come in different shapes and sizes. Image is courtesy of Katja Heuer and Roberto Toro from

Some brains are folded others are smooth, but all mammals have six layered cerebral cortex.  Other vertebrates (turtle, iguana, crocodile, see Figure 2) do not have six layered cortex.

Figure 2: On the cross sections of four different brains I demonstrate the spectacular differences between forebrain organization in A: marsupial, Native Cat, B: Turtle, C: Iguana, D: Crocodile. Note the thicker dorsal cortex in marsupial (A) and the huge ball-like structure in B-D protruding into the lateral ventricle. Abbreviations: ST, striatum; MC, medial cortex; LC, lateral cortex; S, septum; DVR, dorsal ventricular ridge).

Reptiles and birds have no six-layered cortex, but they have an enormous dorsal ventricular ridge. They follow a different brain organization strategy. They can perform extremely well with such structures; see this video on cognitive functions of a crow.

How do these differences in brain organization emerge? Evolution acts on the level of populations, it builds on individual variability and modifications of development that will produce altered adult structures and these will be tested and selected on population level. Evolution does not work as it is portrayed in the “Right here right now” video by Fatboy Slim which demonstrates almost all misconceptions one can have on evolution.

Figure 3: The “Right here right now ” video by FatboySlim portrays a single individual transforming from one adult structure into another during its life. It demonstrates almost all misconceptions we can have on evolution. The music is OK.

How are neurons produced in our brain?  How did neuronal production evolve? What are the differences between a mammal and a reptile or a bird?

Almost all of our neurons for our cerebral cortex are born with us. They are results of neuronal progenitor divisions during our embryonic life. Our nerves system starts as a plate that will form a tube with an inner and outer suface (Figure 4). Since the ventricles are inside the brain, these are called ventricular surface. The outer surface is covered with the basal membrane and the pia mater; therefore, it is called pial surface. Cell divisions occur in ventricular or apical surface of the neuroepithelium. 

Figure 4: The production and assembly of neuronal circuits are different in the avian (A) and mammalian (B) brain. In the avian pallium, different sectors contain different progenitors that produce different elements. In mammals the diverse elements of the functional columns are produced within the same sector of cortical neuroepithelium. In avian brains the neurons that assemble into functional units organized perpendicular to boundaries of initial subdivisions. In mammalian cortex the distinguishable radial columns are formed. Mammalian neurons form columns that extend across the layers of the cerebral cortex perpendicular to the pial surface.

Germinative zones in the pallium of amniote brains display strong conservation prior neurogenesis. However, as soon as neurogenesis starts, pallial neural stem cells in amniotes show regional variations and a general trend to diversify. A diverse and densely-populated embryonic progenitor pool feeds the increased demand in neuronal number of the embryonic brain, as a more elaborated hardware is required for complex information processing. Large brains, populated with more diverse neuronal populations that could assemble in complex circuits enabled the behavioral complexity with advantages, and this has only been achieved by diversification and amplification of output from progenitors. We postulate that these divergences were likely initiated by disparities in the graded expression of morphogenic factors from the telencephalic signalling centers.

Variations in the development of the neural tube enabled the production of the six-layered cerebral cortex or also called neocortex and this enlarged in primates (Figure 5). It is surprising that accumulation of subtle modifications from very early brain development accounted for the diversification of vertebrate brains and the origin of the neocortex.

Figure 5: There is a strong correlation between the increase of upper layer complexity and the increase of progenitor populations between lizard (A), mouse (B) and monkey (C). The left panels depict the distribution of progenitors (pink and yellow) and the right panels represent the layering in the adult. Note the increase in the complexity of upper layers is accompanied with the increase of the progenitor pool during development.

Initially, faint differences of expression of secretable morphogens promote a wide variety in the proportions and organization of sectors of the early brains in different vertebrates. It prompted different sectors to host varied progenitors and distinct germinative zones. These cells and germinative compartments generate diverse neuronal populations that migrate and mix with each other through radial and tangential migrations in a taxon-specific fashion. Together, these early variations had a profound influence on neurogenetic gradients, lamination, positioning, and connectivity.

It is fascinating to explore the evolutionary path of the brain of reptiles, birds and mammals, by comparing the developmental themes and variations that led to the building of the vertebrate brain, with a detailed attention to the cerebral cortex. Variations from early neurogenic stages had a cumulative influence similar to a snowball effect, and were the main cause of vertebrate brain diversification. Cell variety increased by segregating neurogenesis in space and time. The novel progenitor cells produced more numerous and more diverse neurons, which located and connected in different manners partly due to additional contributions of novel migrations of neuronal populations. It is fascinating how evolution could produce such a highly complex and efficient and still evolving structure, our brain.

All this evolutionary process that was not directed, not aiming for any particular organization and took millennia may sound surprising, but it is explained by Daniel Dennett in a brilliant lecture on Information, Evolution, and intelligent Design. This will put the above proposed cellular and molecular changes into context.

Figure 6: Daniel Dennett: Information, Evolution, and intelligent Design

The developmental sector that produce the mammalian neocortex is well identified in mammals and its homologs are also known across vertebrates. This sector evolved its divergent relevance due first to the varied power of signaling centres during development. The differences in size and the action of morphogens promoted the appearance of new precursor cell types. As a consequence, divergent and more populated germinative zones appeared across embryonic brains. Accompanied by novel cell populations, which can also migrate from external sources, the brain evolved to diversify the neuronal production. All these evolutionary variations, together, enabled the variation of development that enabled the production and existence of the neocortex. We are beginning to discover these cellular and molecular factors in a range of animal models. However, much more detailed lineage studies are required to map out the homology of brain structures and unraveling the evolutionary history of our own brains.

If you are interested in this topic, you can watch a lecture from Zoltán on YouTube.

Professor Zoltán Molnár, Tutorial Fellow in Human Anatomy