Kanazawa University Research: Structural Development of the Brain

In a recent study published in The Journal of Neuroscience, researchers reveal how the basic structure of the brain is formed

KANAZAWA, Japan, June 24, 2019 /PRNewswire/ -- The human brain consists of neurons arranged into microscopic columns. The cortex, which is the seat of most cerebral functions and forms the largest part of the brain, is divided into uncountable micro-columns. However, the exact development of this columnar structure is elusive to neuroscientists. A research team led by Makoto Sato, has recently reported their study describing the role of a specific protein in the growth of these columns.

The team spanning across Kanazawa University, Ryukoku University, Tokyo Institute of Technology and Imperial College London, used the Drosophila melanogaster (fruit fly) brain for their experiments. The visual centre of the Drosophila brain bears high structural resemblance to the columnar arrangement of the human one, making it an apposite, yet simple model to study. To first visualize these columns, N-cadherin (Ncad), a protein specific to the nervous system, was mapped. The spatial locations of Ncad revealed that during the larval stage of the fly, the visual centre comprised a donut-like structure. As the fly matured to the pupal stage, these structures started stacking on top of each other and indeed transformed into a three-dimensional column.

The research team then carefully analysed these columns and found the presence of three neuron types, namely, R7, R8 and Mi1 within them. While R7 was concentrated towards the central core of the columns, R8 and Mi1 were arranged towards the periphery. Now that the structural composition was clear, understanding the process of column formation was the next step. It was suspected that Ncad, which was heavily present in the columns, played a role in this regard. When Ncad was measured in all three neuron types, it was found that R7 neurons contained more Ncad than the peripheral neurons. Since Ncad is known to give cells adhesive properties, the team concluded that it was the levels of Ncad which determined the location of each of the neuron types within the columns. Heavily adhesive neurons such as R7 formed the core of the columns.

Lastly, to see whether Ncad directly affected the columnar arrangement, it was either completely removed or greatly increased in the neurons. As expected, manipulation of Ncad disturbed the columnar assembly and positions of the neurons. For example, R7 neurons without any Ncad were no longer within the core. However, when Ncad was greatly increased within them, the R8 and Mi1 neurons extended towards the core, possibly due to the strong adhesive properties of Ncad.

This study revealed the role of an adhesive protein in arranging neurons to form the columnar microstructure of the brain. "[Ncad-dependant] differential adhesion and inter-layer interaction may be the essential mechanism underlying the 3D organization of column formation that is evolutionarily conserved from the fly optic lobe to mammalian brains," conclude the researchers. This discovery can help neuroscientists monitor healthy development of the brain and uncover other molecules involved in the process.

Background:

N-cadherin (Ncad): Ncad is a protein found abundantly in the nervous system. Being an adhesive protein, it regulates cell shape and controls the arrangement of tissues. In the nervous system, Ncad is known to facilitate communication and signal transduction between neurons. This study is the first to demonstrate the role of Ncad in columnar organization during development.

Reference:

Olena Trush, Chuyan Liu, Xujun Han, Yasuhiro Nakai, Rie Takayama, Hideki Murakawa, Jose A. Carrillo, Hiroki Takechi, Satoko Hakeda-Suzuki, Takashi Suzuki, Makoto Sato. N-cadherin orchestrates self-organization of neurons within a columnar unit in the Drosophila medulla. The Journal of Neuroscience, 2019.

https://doi.org/10.1523/JNEUROSCI.3107-18.2019

About Kanazawa University

As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities.

The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas.

Kanazawa University website

http://www.kanazawa-u.ac.jp/e/

Further information

Kanazawa University
Kakuma, Kanazawa, Ishikawa 920-1192, JAPAN
E-mail: intl.pr@adm.kanazawa-u.ac.jp  
Tel: +81(76)264-5076