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 TubeNeural plate

EctodermMesodermEndoderm

Neural grooveParaxial mesoderm

Neural tube

Lateral plate mesoderm

Paraxial mesoderm

NotochordEndoderm

Somite

Early Development of the Vertebrate Central Nervous System

Hox b2 Hox b4

Hox Genes are Expressed in the Developing Neural Tube

The HOM/Hox Gene Clusters

Hindbrain is Segmented by Hox Genes

Hoxb-1Hoxb-2Hoxb-3Hoxb4

KreislerKrox20

EphA4EphA2EphB2EphB3

Ephrin B1Ephrin B2Ephrin B3

Hox genes

Othertranscriptionfactors

Eph kinases

Ephrins

r1 r2 r3 r4 r5 r6 r7

r2 r3 r4 r5 r6

Segmental Expression of Hindbrain Patterning Genes

Segmental Development of the Hindbrain Motor Neurons

TrigeminalNerve (V)

FacialNerve (VII)

Grosso-pharyngealNerve (IX)

Vegus, spinalaccessoryNerve (X, XI)

Somatic motor nuclei Visceral motor nuclei

Oculomotor nerve (III)

Trochlear Nerve (iV)

AbducensNerve (VI)

Hypoglossal Nerve (VII)

r1

r2

r3

r4

r5

r6

r7

r8

Midbrain

Hindbrain

Mutation of Hoxb-1 Causes Homeotic Transformation of the Hindbrain Motor Neurons

r2 v.s. r4 neurons Wild type Hoxb-1 Mutant

Trigeminal nerveexit point

Facial nerveexit point

Trigeminal motor neurons

Facial motor neurons

Hoxb-1

r2 r2

r4

r4 r2

r2

r3

r4

r5

r6

Trigeminal motor neurons

Trigeminal-like motor neurons

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

Confocal micriscopy image of a fly embryo at stage 14

Green dots: cells expressing Engrailed, a segment-polarity gene

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

ホメオドメインのアミノ酸配列の比較

タンパク構造の比較

Human Otx Gene Restores Brain Patterning in　 Drosophila otd Mutant

The Drosophila otd Genes Restores Brain Patterning in Mouse Otx Mutants

WT Otx-/-

Otx-/-

WT

Rescue with Fly otd gene

Genetic 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• 第 1巻　脳の計算論• 第 2巻　認識と行動の脳科学• 第 3巻　言語と思考を生む脳• 第 4巻　脳の発生と発達• 第 5巻　分子・細胞・シナプスからみる脳• 第 6巻　精神の脳科学

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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