Brain Development and
Evolution
Genetic Factors Underlie Human Behaviors
Genes
Neurons
Networks
Behaviors
Neuroscience
The goal of neural science is to
understand the mind – how we
perceive, move, think, and
remember.
Eric Kandel
Nobel Prize
in Physiology or Medicine 2000
Behavior can be examined at the
level of individual nerve cells by
answering
five basic questions.
1. How does the brain develop?
2. How do nerve cells in the brain communicate with
one another?
3. How do different patterns of interconnections give
rise to different perceptions and motor acts?
4. How is communication between neurons modified
by experience?
5. How is that communication altered by diseases?
Development of Vertebrate Neural Tube
Neural plate
Ectoderm
Mesoderm
Endoderm
Neural groove
Paraxial
mesoderm
Neural tube
Paraxial
mesoderm
Lateral plate
mesoderm
Somite
Endoderm
Notochord
Early Development of the Vertebrate Central
Nervous System
Hox Genes are Expressed in the
Developing Neural Tube
Hox b2
Hox b4
The HOM/Hox Gene Clusters
Hindbrain is
Segmented by
Hox Genes
r1
r2
r2
Segmental
Expression of
Hindbrain
Patterning
Genes
Hox genes
Hoxb-1
Hoxb-2
Hoxb-3
Hoxb4
Other
transcription
factors
Kreisler
Krox20
Eph kinases
Ephrins
EphA4
EphA2
EphB2
EphB3
Ephrin B1
Ephrin B2
Ephrin B3
r3
r3
r4 r5 r6 r7
r4
r5
r6
Somatic motor nuclei
Oculomotor
nerve (III)
Visceral motor nuclei
Midbrain
Trochlear
Nerve (iV)
Segmental
Development
of the
Hindbrain
Motor
Neurons
Hindbrain
r1
r2
Trigeminal
Nerve (V)
r3
r4
Abducens
Nerve (VI)
Facial
Nerve (VII)
r5
r6
Grossopharyngeal
Nerve (IX)
r7
Hypoglossal
Nerve (VII)
r8
Vegus, spinal
accessory
Nerve (X, XI)
Mutation of Hoxb-1 Causes Homeotic
Transformation of the Hindbrain Motor Neurons
r2 v.s. r4 neurons
Wild type
Trigeminal nerve
exit point
Trigeminal
motor neurons
Trigeminal
motor neurons
r2
r2
Facial nerve
exit point
Hoxb-1 Mutant
r3
r4
r5
r6
Facial motor
neurons
r2
Trigeminal-like
motor neurons
r4
Hoxb-1
r4
r2
HOM/Hox Genes Fail
to Cover the Most
Anterior Region of the
Central Nervous
System.
What Kind of Genes
Specify the Brain??
The Drosophila Central Nervous System
is Segmented
Green dots: cells expressing Engrailed, a
segment-polarity gene
Confocal micriscopy image of a fly embryo at stage 14
ショウジョウバエ胚における分節遺伝子
engrailedの発現
Fruit Fly Brain at Stage 14 (10 hours)
Green: neurons. Red: Brain Specific Homeobox Protein.
Blue：major axonal tracts stained with anti-FAS II
Homeobox-Containing Genes, otd and ems,
Control Segmental Organization of the Embryonic
Fly Brain
otd/Otx and ems/Emx Genes Control the
Formation of the Vertebrate Brain
Genetic Programs of Brain Development are
Evolutionary Conserved between Flies and
Vertebrates
Structures of Drosophila, Human and Ascidian
otd/Otx Genes
タンパク構造の比較
ホメオドメインのアミノ酸配列の比較
Human Otx Gene Restores Brain Patterning in
Drosophila otd Mutant
The Drosophila otd
Genes Restores
Brain Patterning
in Mouse Otx
Mutants
Otx-/WT
Genetic Rescue with
Fly otd gene
WT
Otx-/-
Rescue with
Fly otd gene
Cross-Phylum Conservation of Major Axonal
Tracts between Flies and Vertebrates
Drosophila
Zebrafish
Inversion of Dorso-Ventral Patterns between
Protostomes and Deuterostomes
Arthoropods
Vertebrates
Despite the Apparent Inversion, Genetic Programs
of Brain Development is Evolutionary Conserved
Common Origin of the Animal Brain
Neuroscience Text Books
• Principles of Neuroscience, 5th ed. 2012, Kandel, E. R.,
Schwartz, J. H., Jessel, T. M., Siegelbaum, S. A., and
Hudspeth, A. J., McGrae Hill.
• Physiology of Behavior, 10th ed, 2009, Carlson, N. R. ,
Allyn & Bacon. カールソン 神経科学テキスト 脳と行動、
2010、丸善。
• Fundamental Neuroscience, 3rd ed, 2008, Squire L.R et
al., Academic Press.
Neuroscience Focuses on
Molecular Genetic and
Behavioral Problems
Fundamental Neuroscience
53 Chapters
Electrophysiology
3
Genes and Molecules
51
Behavior and Cognition 10
シリーズ脳科学 東京大学出版会
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脳の計算論
認識と行動の脳科学
言語と思考を生む脳
脳の発生と発達
分子・細胞・シナプスからみる脳
精神の脳科学
• 新・脳の探検、上下、ブルーバックス．
• 記憶と情動の脳科学、ブルーバックス．
• 私の脳科学講義、利根川進、岩波新書．
ショウジョウバエ胚の脳（レーザ共焦点顕微鏡画像）
Eyeless &Twin of Eyeless