熊本大学発生医学研究所／ P19-20 【英訳】Division of Organogenesis

Brain Morphogenesis

In pursuit of the mystery andcomplexity of brain development
Unveiling the mechanisms underlying the creationof the “control tower” of the organism
A map for brain formation is determined in the early stages of embryogenesis.
Based on this map, the various domains in the brain are formed, and eventually each domain comes tohave distinct and specific characters and functions.
Dr. Kenji Shimamura’s research sheds light on the sophisticated and dynamic mechanisms underlying theformation of our high-functioning brains.

ProfessorKenji Shimamura
simamura@kumamoto-u.ac.jp

Searching for the mechanisms
determining the properties anddestination of neurons and thearchitectures of each brain tissue
according to the map of the brain
The mechanisms by which our brains, highly functioning“control towers” that determine our every activity, areformed remain deeply mysterious and to be understood.
Yet this puzzles is exactly what Dr. Kenji Shimamura
busies himself with in his research, focusing in particularon how and where neurons are formed, as well as how thevarious areas of the brain come to develop according to
the data setting out the map of the brain.
The neural plate appears at a very early stage inembryogenesis, and is made up of epithelial cells, the stem
cells of the central nervous system. It is here, on this sheetof cells, that the map of the brain has been imprinted. “Thebehavior of neurons is determined by the instructions
found in this map; first, the areas of the brain such as thecerebrum and the cerebellum are formed. Research has
already revealed the basic principles by which the brain
map is imprinted onto this brain primordium, the neuralplate, and the mechanism by which different neurons with
distinct characteristics are generated according to theposition in the brain,” says Dr. Shimamura. There is stillmuch we do not know, however, for example how eacharea goes about forming the structure required of it by thebrain map.

Processes to control proliferationand differentiation and to create
differences in tissue architecture.

References●Sato, H., Fukutani, Y., Yamamoto, Y., Tanaka,E., Ta ke m oto, M.,S h i m a m u r a , K . a n dYamamoto, N. Thalamus-derived molecules
promote survival and dendritic growth ofdeveloping cortical neurons. J. Neurosci.
32,15388-15402, 2012.
●Hashimoto-Torii, K., Motoyama, J., Hui, C.,
Kuroiwa, A., Nakafuku, M. and Shimamura,
K. Differential activities of Sonic hedgehog
mediated by Gli transcription factors define
distinct neuronal subtypes in the dorsal
thalamus. Mech. Dev. 120, 1097-1111,2003.
●Kobayashi, D., Kobayashi, M., Matsumoto,K., Ogura, T., Nakafuku, M. and Shimamura,
K. Early subdivision in the neural plate define
distinct competence for inductive signals.
Development 129, 83-93, 2002.

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temporal changes in the basic mechanism are behindthese differences.” This would suggest that, for example, in
one position in the brain, the formation of a large volumeof neurons in a short time results in cluster-like tissue,
while in another position, the pace of production is slower,
allowing the neurons to gradually form sheets over time.
Dr. Shimamura continues to press forward with his
examination of this assumed mechanism.

Next, neurons move away from their birthplace and movetoward their destination, building brain tissue in theprocess. Dr. Shimamura speculates that the pace ofneuron production must be linked in some way todifferences in the internal structures formed after theneurons have moved position. “The neurons start to build
up, thickening the walls of the brain, but while in someareas neurons will stack up in layers, in others the neurons
form exquisite clusters. The basic mechanism of neuron
production remains the same, yet differences emerge inthe tissue they form; we believe that quantitative andThis cerebral neocortex is only observed in mammals,including humans; it does not appear to be present inother vertebrates, including birds and reptiles. By
investigating the mechanisms that cause tissuemorphology to change according to brain region, Dr.
Shimamura hopes to be able to clarify the mechanisms bywhich different brain structures among the vertebrate
species. “I would like to further our understanding of
brain morphogenesis, in the hope of advancing ourunderstanding of the mysteries of brain evolution”.

Cytoarchitecture of the cortical areas and the roles of input fibersVisualSomatosensory
Auditory

ProfileBorn in 1965, in Hyogo prefecture.
Graduated with a Bachelor s degree from the Faculty ofScience, Kyoto University, then went on to complete
Master s and Doctoral degrees at the Graduate School ofScience at the same university. Holds a Ph.D.
In 1994, he took up a position as a research fellow at theDepartment of Psychiatry, University of California, SanFrancisco in the United States.
In 1997, he moved back to Japan to become a seniorassistant professor at the Department of Neurobiology,
Graduate School of Medicine, The University of Tokyo.
In 2002, he became a professor at the Institute of
Molecular Embryology and Genetics, Kumamoto University.

Neural stem cells divide rapidly, and the outcome ofdivision varies: in some cases, both daughter cells arisingfrom division will have the same characteristics as theparent cell (proliferation); in other cases, one cell will beidentical to the parent cell (self replication) while the otherbecomes a neuron (differentiation); in still others, bothdaughter cells will be neurons. This principle applies toevery area of the brain, but the numbers of neurons andneural stem cells produced, and the ratio between them,varies according to position in the brain. This balance isalso affected by the stage of development. “We believe
there must be mechanisms regulating the balance
between neuron production and neural stem cellproliferation according to position and developmental
stage,” states Dr. Shimamura. One possible mechanism, hesuggests, is based on the contact between parent anddaughter cells: daughter cells that have become neurons
release the contact quickly away from the parent cell,allowing that cell to continue to differentiate rapidly, whilethose daughter cells that retain the contact with the parent
prevent the parent cell from differentiating, prompting it
instead to proliferate. His research seeks to verify thishypothesis, in which daughter cells regulate thedifferentiation and proliferation of parent cells.

Towards the mysteries of evolution:
the mechanism of cerebral neocortex
formation
The cerebral neocortex, which contains a number ofsignificant regions including the motor, language, visual,and auditory cortices, is made up of six layers. We alreadyknow that these layers differ in structure and thickness
throughout the various cortices. “So although we know
how the cortices are determined, we don’t yet know why
different structures are formed. Sensory information istransmitted to the neocortex, via the neural fibers derived
from thalamic nuclei. What we think is that, at this point,something within the neural fibers may control theformation of layer structure of the target cortical areas”.

Control of the pace of neuron production
Neurons maintainadherens junctions
with neighboringprogenitors.

Motor

Neural progenitors
stay undifferentiated.
Apical process ofneuron.
Major cortical areas projectedfrom the thalamus.
Thalamic axons determine thestructural differences between
cortical areas.

dLGN
VBMG

Neurons inactivate
adherens junctions.

Neuroal progenitors
differentiate intoneurons.
The apical endfoot ofneuron is detached.

VAL

Time-lapse observations of neural stem cells
Adherens junction

Teaching Staff
Assistant Professor

Jun Hatakeyama
The developmental processes by which the brain forms, startingwith a single homogenous sheet of neuroepithelia, is truly
mysterious. My research looks at the building processes seen inbrain formation, which I examine using mouse and chicken
embryos. Through my research, I hope to share the joy ofwitnessing the formation of life with many people. How are ourbrains made? How have they evolved? I look forward to hearing
from students who are willing to tackle these questions with me!

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