1. Developmental Biology (BS318) -Professor: Dae-Sik Lim (BMRC (E7), Tel. 2635, e-mail: daesiklim@kaist.ac.kr)daesiklim@kaist.ac.kr -Time: Monday & Wednesday (2:30 pm – 4:00 pm) -Lecture Rm: Creative Study Building Rm. 창의 406 -The course is designed for the students who had already taken General Biology, Biochemistry, Molecular Biology, Cell Biology, and Genetics. -Text: Developmental Biology (by Scott F. Gilbert, 9 th edition, Sinauer Inc.) -Supplements: Principle of Development (L Wolpert; Oxford), -Grading: 1st Exam (40% -  ) + Final Exam (40% -  ) + Attendance/Class Activities/Term Subjects (20% +  ) - T.A.: Haeyon Jeon (T. 2675; e-mail: haeyonjeon@gmail.com )haeyonjeon@gmail.com

2. We are humans Sometimes we look same

3. We look different from other animals

4. But, we were not that different from others

5. Development is a fundamental part of biology Developmental Biology deals with complex mechanisms and many layers of "biological information" superimposed one upon another. Goal of Dev Bio is to understand how genes control embryonic development. Recent advances in cell biology, genetics and molecular biology has and will continue to further unlike any time in the past. our understanding of development Embryogenesis (embryo formation) determines the overall body plan. Organogenesis (organ formation) determines subsections of the body (examples: vertebrate limb, Heart, Drosophila eye). Many genes, proteins, signal transduction pathways and cell behaviours are common to both processes. Development is a fundamental part of biology

6. Development Underlying process that gives rise to the structure and function of living organisms Refers to a series of changes in the state of the cell, tissue, organ, or organism Developmental genetics aimed at understanding how gene expression controls this process

7. Historical views on the development Epigenesis ( Aristotle theory): is a theory of development that states that new structures arise by progressing through a number of different stages. Preformation theory (Rene Decart’s idea of infinitely dividing life) - all organs had been already generated in the germ cells, then they just grow during developmental periods - miniature life in the egg or sperm

8. Historical views on the development Immanuel Kant and Johann Friedrich Blumenbach - Bildungstrieb ( developmental force ) is inheritable and also variable. Cell Theory: Schleiden and Schwan 1820-1880 Organisms are composed of cells, the basic unit of life. We are multicellular composites that arise from a single cell, therefore development must be epigenetic and not preformational since a single cell (the fertilized egg) results in many different types of cells. Only the germ cells (egg and sperm) pass characteristics on to the offspring. Somatic cells are not directly involved in passing on traits to the next generation and characteristics acquired during an animal's life are not passed onto the offspring. Current understanding - Developmental force is genetic information

9. Developmental Biology: The Anatomical Transition Main questions of Developmental Biology 1.Differentiation 2.Morphogenesis 3.Growth 4.Reproduction 5.Regeneration 6.Evolution 7.Environmental integration

10. Life Cycle The Circle of Life: The stages of animal development -Life has been already started upon the fertilization, even we couldn’t see that! -Embryogenesis: events after fertilization until hatching or born -Cleavage: forms blastomeres -Cell movement: lead to gastrula stage with distinct germ layers -Forming specific structures using the various cells: organogenesis (local formation or migration) -Massive changes into sexually mature adults: morphogenesis -Full maturation and modification: metamorphosis -Differentiation into gametes (sperm or egg): gamatogenesis

11. Developmental history of the leopard frog, Rana pipiens

12. 2 Early Xenopus development: fertilization The unfertilized egg is a single large cell. The animal pole, the upper part of the egg, has a pigmented surface. The vegetal pole, lower region, contains the yolk. After fertilization, the male nucleus (from sperm) and female nucleus (from egg) fuse to form one nucleus. After fertilization, cleavage begins without growth (mitotic division only).

13. 2 Xenopus blastulation After ~12 cycles of division a layer of small cells is formed surrounding a fluid-filled cavity (the blastocoel) that sits on top of the large yolk cells. Three germ layers are mesoderm, endoderm and ectoderm The mesoderm is located at the "equator" and becomes muscle, cartilage, bone, heart, blood, kidney The endoderm is above the mesoderm and below the ectoderm and becomes gut, lungs and liver The ectoderm sits above the endoderm and becomes the epidermis and nervous system In the blastula, these layers are all on the surface and they interact!

14. 2 Xenopus gastrulation & neuralution Gastrulation is an extensive rearrangement of embryonic cells. Mesoderm and endoderm move to the inside of the embryo to give the basic body plan. For the most part, the inside of the frog is now inside and the "outside" except for the skin is outside. Notochord is a rod-like structure that runs from the head to the tail and lies beneath the nervous system. Somites are segmented blocks of mesoderm which form on either side of the notochord. They become muscles, spinal column and dermis (skin). Neuralation occurs when ectoderm above the notochord folds to form neural tube (becomes spinal cord & brain).

15. Continued development of Xenopus laevis (Part 3)

16. Metamorphosis of the frog

17. 2 Five processes of development 1. Cleavage Division: No increase in cell mass 2. Pattern Formation: A/P and D/V axes: Coordinate system 3. Morphogenesis: take 3D form, neural crest migrates far. 1 egg - 250 types 4. Cell Differentiation: cells become structurally and functionally different. 5. Growth: cell multiplication, increase in cell size, deposit extracellular material (bone, shell) growth can be morphogenetic.

18. Some representative differentiated cell types of the vertebrate body

19. 2 Five cell behaviours Gene expression results in cell behaviour and development. Gene activity gives cell identity. 1. Cell-cell communication 2. Cell shape changes 3. Cell movement 4. Cell proliferation 5. Cell death (apoptosis)

22. Similarities/differences among different vertebrate embryos through development

23. Evolutionary embryology - Homologies of structure

24. Divergence of structures – evolutionary change

25. Selectable variation The Dachshund: "badger( 오소리 ) dog" Extra copy of fgf4: 연골발육부전증 (Achondrodysplasia) Premature end of cell proliferation of in the limb cartilage precursor cells Truncated Fgf5 - alters hair follicle cycles, long hair formation

26. Developmental anomalies caused by genetic mutation Piebaldism upon mutations of KIT gene both human and mouse

27. Developmental anomalies caused by an environmental agent Taking thalidomide during pregnancy - it was used against nausea and to alleviate morning sickness in pregnant women -50 percent of the mothers with deformed children had taken thalidomide during the first trimester of pregnancy -Thalidomide binds to and inactivates the protein cereblon, which is important in limb formation and leads to a teratogenic effect on fetal development ????

28. Fate mapping using a fluorescent dye (Part 1)

29. Fate mapping using a fluorescent dye (Part 2)

30. Genetic markers as cell lineage tracers

31. Neural crest cell migration

32. Fate mapping with transgenic DNA