The developing brain

Investigating how the normal brain develops to improve treatment for patients with brain injury

It is estimated that more than half of the genes in the genome are used in building the brain, far more than are used for any other organ system

The human brain is composed of about 10 billion individual neurons and more than a trillion synapses. Research groups all over the world have been working on how it is that such an unbelievably complex biological machine can be built so that it works “when you open up the box”. The answer lies in the immensely sophisticated development of the nervous system. It is estimated that more than half of the genes in the genome are used in building the brain, far more than are used for any other organ system.

The developmental neuroscience community in Cambridge is made up of a diverse group of researchers spanning the Departments of Biochemistry, Clinical Neurosciences, Genetics, Physiology, Development & Neuroscience, Psychiatry and Zoology, as well as the internationally recognised Gurdon Institute of Developmental Biology and the new Centre for Stem Cell Research. These teams are approaching major issues in neural development at a variety of levels. How are genes involved in determining neuronal fate? How can pluripotent stem cells, which have the capacity to become different germ cell layers, become specified to differentiate as particular types of neurons? How is the cell-cycle controlled so that brains grow to the right size? How are instinctive behaviours wired into the developing brains? What are the molecules that guide the axons of neurons to their distant postsynaptic targets? How are synapses made and adjusted? When a human or an animal is born, the brain works properly because of huge developmental investment. But when an adult brain is damaged by accident or disease, it usually does not completely heal, probably because the developmental mechanisms that are needed are not reactivated in adults.

Researchers at Cambridge are increasing understanding on how the brain develops to identify new ways to repair the damaged brain

Multidisciplinary work at Cambridge is making substantial inroads into all of these and many other fascinating questions of brain development. Researchers at Cambridge are working on the principle that basic research into the molecular mechanisms of normal brain development will be key to finding ways to repair the damaged brain. Hence much of the research in developmental neurobiology has clear and important links between basic and clinical research. It is this attitude that has set the stage for building links to biotechnology. DanioLabs, a highly successful drug-discovery spin-out company from the developmental neurobiology community in Cambridge, is an example of the success of this approach. DanioLabs have been pioneering the use of tiny developing zebrafish embryos to model and identify cures for different brain injuries and dysfunctions, including neurodegenerative diseases, multiple sclerosis, epilepsy, bipolar disease, neuropathic pain and even headaches.

A recent collaboration between researchers in the Departments of Biochemistry and Physiology, Development & Neuroscience, showed that the gradient of an axon guidance molecule, known as Netrin-1, triggers a polarized increase in beta-actin translation on the near side of growing axons, causing them to turn towards the Netrin-1 source. Inhibition of betaactin translation abolishes both the asymmetric rise in beta-actin filaments and Netrin-1 guidance. Thus, newly synthesized beta-actin, concentrated near sites of signal reception, provides the bias for attractive turning. These exciting findings, recently published in Nature Neuroscience, provide deep insight into the cellular machinery used by axons to navigate in the developing brain.