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Brain Development and Evolution. Genetic Factors Underlie Human Behaviors.

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Presentation on theme: "Brain Development and Evolution. Genetic Factors Underlie Human Behaviors."— Presentation transcript:

1 Brain Development and Evolution

2 Genetic Factors Underlie Human Behaviors

3 Genes Neurons Networks Behaviors

4 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

5 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?

6 Development of Vertebrate Neural Tube Neural plate Ectoderm Mesoderm Endoderm Neural groove Paraxial mesoderm Neural tube Lateral plate mesoderm Paraxial mesoderm Notochord Endoderm Somite

7 Early Development of the Vertebrate Central Nervous System

8 Hox b2Hox b4 Hox Genes are Expressed in the Developing Neural Tube

9 The HOM/Hox Gene Clusters

10 Hindbrain is Segmented by Hox Genes Hoxb-1 Hoxb-2 Hoxb-3 Hoxb4 Kreisler Krox20 EphA4 EphA2 EphB2 EphB3 Ephrin B1 Ephrin B2 Ephrin B3 Hox genes Other transcription factors Eph kinases Ephrins r1 r2 r3 r4 r5 r6 r7 r2 r3 r4 r5 r6 Segmental Expression of Hindbrain Patterning Genes

11 Segmental Development of the Hindbrain Motor Neurons Trigeminal Nerve (V) Facial Nerve (VII) Grosso- pharyngeal Nerve (IX) Vegus, spinal accessory Nerve (X, XI) Somatic motor nuclei Visceral motor nuclei Oculomotor nerve (III) Trochlear Nerve (iV) Abducens Nerve (VI) Hypoglossal Nerve (VII) r1 r2 r3 r4 r5 r6 r7 r8 Midbrain Hindbrain

12 Mutation of Hoxb-1 Causes Homeotic Transformation of the Hindbrain Motor Neurons r2 v.s. r4 neuronsWild typeHoxb-1 Mutant Trigeminal nerve exit point Facial nerve exit point Trigeminal motor neurons Facial motor neurons Hoxb-1 r2 r4 r2 r3 r4 r5 r6 Trigeminal motor neurons Trigeminal-like motor neurons

13 HOM/Hox Genes Fail to Cover the Most Anterior Region of the Central Nervous System. What Kind of Genes Specify the Brain??

14 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

15 ショウジョウバエ胚における分節遺伝子 engrailed の発現

16 Fruit Fly Brain at Stage 14 (10 hours) Green: neurons. Red: Brain Specific Homeobox Protein. Blue : major axonal tracts stained with anti-FAS II

17 Homeobox-Containing Genes, otd and ems, Control Segmental Organization of the Embryonic Fly Brain

18 otd/Otx and ems/Emx Genes Control the Formation of the Vertebrate Brain

19 Genetic Programs of Brain Development are Evolutionary Conserved between Flies and Vertebrates

20 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

21 Human Otx Gene Restores Brain Patterning in Drosophila otd Mutant

22 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

23 Cross-Phylum Conservation of Major Axonal Tracts between Flies and Vertebrates Drosophila Zebrafish

24 Inversion of Dorso-Ventral Patterns between Protostomes and Deuterostomes Arthoropods Vertebrates

25 Despite the Apparent Inversion, Genetic Programs of Brain Development is Evolutionary Conserved

26 Common Origin of the Animal Brain

27 Neuroscience Text Books Principles of Neuroscience, 5 th ed. 2012, Kandel, E. R., Schwartz, J. H., Jessel, T. M., Siegelbaum, S. A., and Hudspeth, A. J., McGrae Hill. Physiology of Behavior, 10 th 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, 3 rd ed, 2008, Squire L.R et al., Academic Press.

28 Neuroscience Focuses on Molecular Genetic and Behavioral Problems Fundamental Neuroscience 53 Chapters Electrophysiology 3 Genes and Molecules 51 Behavior and Cognition 10

29 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.

30 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

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