#BAW2016: “The birth of consciousness: a story of brain creation” by Shane Hegarty

March 14, 2016 PLOS Blogs Basic Neuroscience Neuroscience

‘I think therefore I am’. While René Descartes’ profound quote may underestimate the elusive existential truth of what makes us human, brain creation is intrinsically linked to human creation.

Have you ever wondered how your brain is created? The answer emanates from the microscopic, but miraculous, embryo. Succeeding the unlikely event of reproduction, the embryo consists of multiplying stem cells that can become any human cell type. Once inside the womb, stem cells choose one of three fundamental cell fates: ecto-(outer), meso-(middle) or endo-(inner) derm (cell layer). The three-week-old embryo consists solely of these three cell layers. The outer ectoderm eventually becomes outer-body parts (skin/hair/teeth), the middle mesoderm develops into bones, muscles and blood vessels, while the inner endoderm layer forms our inner-body compartments (gut/lungs). So where does our brain come from?

Figure 1: Embryo stem cell becomes ectoderm, mesoderm or endoderm cell layers.

To state that embryo stem cells are deciding their fate is not entirely accurate. In fact, the surrounding environment largely dictates what these stem cells become, with neighbouring cells sending ‘chemical’ messages to nearby stem cells to instruct their destiny. Our brain arises as a result of such instructive interactions. To spare us scientific jargon, brain creation will be compared to the ‘creation of brain-iness’ in school. In this curious analogy, a specialised rod of mesoderm is the teacher, while the overlying ectoderm cells are students. This rod sends a suitably-named chemical message ‘Noggin’ towards the ectoderm, similar to how a teacher instructs students to ‘use their noggin’. Students that choose to listen to their teacher’s instruction, usually sitting eagerly right in front of the teacher, become ‘brainy’. Similarly in the embryo, ectoderm cells which lie directly above the mesoderm rod respond to Noggin instructions and become ‘brain stem cells’. However, distant ectoderm cells do not respond to Noggin sent from the instructive mesoderm rod, and thus do not become brain stem cells.

Figure 2: Neural plate (brain stem cells) and neural crest (neural crest cells) form from the ectoderm in response to ‘Noggin’ released by underlying specialised rod of mesoderm.

Important brain-like cells also arise at the border between ectoderm and brain cells by marginally responding to Noggin. These ‘neural crest cells’ travel to different body parts to become ‘peripheral’ brain cells, and have a variety of functions depending on where they end up. For example, neural crest cells which travel to our heart settle there to control its beating, while those that get stuck in the gut control our digestion.

At this point of our embryonic journey, the brain stem cells, capable of becoming any type of brain cell, are collectively known as the ‘neural plate’. This plate quickly expands, curls-up and then folds-in on itself to form the ‘neural tube’. The neural tube runs from head to tail(-bone) along the centre of the embryos’ back, and is the precursor of our brain and spinal cord. When the neural tube forms it literally ‘gets under our skin’, by detaching from the ectoderm, and then positioning itself below the ectoderm and above the mesoderm.

Figure 3: Neural plate expands, curls-up and then folds-in on itself to form the neural tube, which then lies under the ectoderm and above the mesoderm.

This ‘muscular’ mesoderm then ‘forces’ the overlying brain stem cells in the front neural tube region to turn into ‘motor’ brain cells, which trigger our muscles movements. The ‘outside/environmental’ ectoderm ‘sensitively asks’ underlying brain stem cells in the back neural tube region to become ‘sensory’ brain cells, which sense touch, pain and position from our environment.

Figure 4: Mesoderm instructs front neural tube brain stem cells to become motor brain cells through Sonic Hedgehog signals, while the ectoderm instructs back neural tube brain stem cells to become sensory brain cells through BMP (‘Be-My-Partner’) signals.

Unique signals at the embryos’ head region instruct the exponential growth of the top-end of the neural tube, which will eventually become the brain. The continuous swelling of this developing brain, due to multiplication and growth of brain cells, results in splitting of the brain vesicle into two cerebral hemispheres. By birth, the brain has grown so large that it is forced by the skull to fold-in on itself, giving the brain its ‘ridgey’ appearance.

Figure 5: Unique signals instruct swelling of neural tube at head region, and this developing brain then expands and splits into two cerebral hemispheres.

Unique head signals also direct generation of the frontal, parietal, temporal and occipital lobes, each having a generalised function (e.g. occipital lobe for vision). Within the different lobes of the brain, there are a number of brain regions which have specific roles (e.g. hippocampus for memory). To make things even more complex, throughout the brain different populations of cells are formed that carry out particular tasks. To put these brain subdivisions into perspective, imagine our brain as the world, lobes as its continents, brain regions as countries and brain cell populations as cities. Individual brain cell populations send-out nerve fibers that connect with a number of other populations, like motorways between major cities. Depending on their ‘neurotransmitters’, brain cells either switch-on or turn-off the cells they communicate with.

Figure 6: The different brain lobes, regions and populations interconnect via nerve fibers.

The crowning part of our brain, called the ‘cerebral cortex’, is responsible for conscious thought. Buried beneath are the ‘animalistic’ parts of our brain, which are unconscious and function in emotion, motivation, memory and sleep. Between the brain and spinal cord is the ‘brain stem’, where brain cell populations that gift us our five special senses reside. Sitting on its back is the ‘cerebellum’ that controls balance and coordination. Below the brain stem, the spinal cord is responsible for the movement and sensation of our body. The creation of connections within this nervous system allows the brain to control, and interpret information from, the entire body. These connections develop in such a way that a map of our entire body, called the ‘homunculus’, forms in the cortex, which is strangely upside-down and disproportionate. What is even more peculiar about the way our brain connects with the body is that the right hemisphere controls the left side of our body, and vice versa.

Figure 7: The brain’s map of the body, known as the ‘Homunculus’ (i.e. ‘little man’).

The precision at which this marvellous community of ~100 billion brain cells is formed is no less than a miracle. Its biological brilliance reflects millions of years of evolutionary adaptations and masterful developmental processes. The brain is responsible for our experience of, and acts as the interface between, the self and the outside world. It constructs our memories of the past and our visions of the future. Everything we think, feel, remember and dream is written by these brain cells. It is almost incomprehensible how amazing our brains really are. But thanks to our brain’s intellect, we can aspire to appreciate its magnificence.

Shane Hegarty is a Post-Doctoral Research Fellow in the Department of Anatomy and Neuroscience, University College Cork, Ireland. His research aims to understand the molecular and cellular mechanisms regulating the survival and growth of midbrain dopaminergic neurons, the cells which progressively degenerate to cause Parkinson’s disease, with the aim of developing novel disease-modifying therapies for the disease.
You can follow him on twitter @SVH_neuro