Brain Development and Evolution. Genetic Factors Underlie Human Behaviors.
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Transcript of Brain Development and Evolution. Genetic Factors Underlie Human Behaviors.
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
• 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