The Genetic Basis of Development

2. The Genetic Basis of Development How do cells with the same genes grow up to be so different?

3. (b) Tadpole hatching from egg (a) Fertilized eggs of a frog Figure 21.3a, b Three Procceses of Development • The transformation from a zygote into an organism • Results from three interrelated processes: cell division, cell differentiation, and morphogenesis

4. Through a succession of mitotic cell divisions • The zygote gives rise to a large number of cells • In cell differentiation • Cells become specialized in structure and function • Morphogenesis encompasses the processes • That give shape to the organism and its various parts

5. (a) Animal development. Most animals go through some variation of the blastula and gastrula stages. The blastula is a sphere of cells surrounding a fluid-filled cavity. The gastrula forms when a region of the blastula folds inward, creating a tube—a rudimentary gut. Once the animal is mature, differentiation occurs in only a limited way—for the replacement of damaged or lost cells. Gut Cell movement Zygote (fertilized egg) Eight cells Blastula (cross section) Gastrula (cross section) Adult animal (sea star) Cell division Morphogenesis Observable cell differentiation (b) Plant development. In plants with seeds, a complete embryo develops within the seed. Morphogenesis, which involves cell division and cell wall expansion rather than cell or tissue movement, occurs throughout the plant’s lifetime. Apical meristems (purple) continuously arise and develop into the various plant organs as the plant grows to an indeterminate size. Seed leaves Shoot apical meristem Root apical meristem Zygote (fertilized egg) Two cells Embryo inside seed Plant Some key stages of development in animals and plants

6. Differential gene expression • Nearly all the cells of an organism have genomic equivalence, that is, they have the same genes • Differences between cells in a multicellular organism • differences in gene expression • not from differences in the cells’ genomes

7. 0 Cell Differentiation • yields a variety of cell types • each expressing a different combination of genes • multicellular eukaryotes • cells become specialized as a zygote develops into a mature organism

8. Muscle cell Pancreas cells Blood cells 0 Cell Diferentiation • Different types of cells • Make different proteins because different combinations of genes are active in each type

9. 0 Differentiated cells • may retain all of their genetic potential • Most retain a complete set of genes • May be totipotent

10. CONCLUSION EXPERIMENT RESULTS Totipotency in Plants Transverse section of carrot root Fragments cultured in nutrient medium; stirring causes single cells to shear off into liquid. 2-mg fragments Plantlet is cultured on agar medium. Later it is planted in soil. Embryonic plant develops from a cultured single cell. Single cells free in suspension begin to divide. A single Somatic (nonreproductive) carrot cell developed into a mature carrot plant. The new plant was a genetic duplicate(clone) of the parent plant. Adult plant At least some differentiated (somatic) cells in plants are toipotent, able to reverse their differentiation and then give rise to all the cell types in a mature plant.

12. DNA doublehelix(2-nmdiameter) Histones Linker “Beads ona string” TEM Nucleosome(10-nm diameter) Supercoil (300-nm diameter) Tight helical fiber(30-nm diameter) 700 nm TEM Metaphase chromosome DNA packing in a eukaryotic chromosome • Wound around clusters of histone proteins, forming a string of beadlike nucleosomes • This beaded fiber is further wound and folded • DNA packing tends to block gene expression • Presumably by preventing access of transcription proteins to the DNA

13. 0 An Extreme Example of DNA Packing X chromosome inactivation in the cells of female mammals Two cell populationsin adult Early embryo Cell divisionand randomX chromosomeinactivation Active X Orangefur X chromosomes Inactive X Inactive X Black fur Active X Allele fororange fur Allele forblack fur

14. Nuclear Transplantation The nucleus of an unfertilized egg cell or zygote is replaced with the nucleus of a differentiated cell

16. How to Clone a SheepBill Ritchie (Produced for the 1997 Royal Agricultural Show) • The Egg • The unfertilized eggs are flushed out of a sheep which has been induced to produce a larger than normal number of eggs. • The Cell • Previously a sample of tissue was from the udder of a six year old ewe was taken and cultured in a dish (Dolly 1). • The cultured cells are starved to send them into a resting or quiescent state. • The fusion • A cell is placed beside the egg and an electric current used to fuse the couplet.

17. How to Clone a Sheep • Culture • The reconstructed embryo is put into culture and grows for seven days. • Development • Embryos which grow successfully are taken and transferred to a sheep which is at the the same stage of the oestrus cycle as the egg. • The sheep becomes pregnant and produces a lamb after 21 weeks (Dolly).

18. Figure 21.8 “Copy Cat” • Was the first cat ever cloned

19. The Stem Cells of Animals • A stem cell • Is a relatively unspecialized cell • Can reproduce itself indefinitely • Can differentiate into specialized cells of one or more types, given appropriate conditions

20. Embryonic stem cells Early human embryo at blastocyst stage (mammalian equiva- lent of blastula) Adult stem cells From bone marrow in this example Pluripotent cells Cultured stem cells Different culture conditions Different types of differentiated cells Blood cells Embryonic and Adult Stem Cells • Stem cells can be isolated • From early embryos at the blastocyst stage • Adult stem cells • pluripotent, able to give rise to multiple but not all cell types Totipotent cells Liver cells Nerve cells

21. 0 Transcriptional Regulation of Gene Expression During Development • Complex assemblies of proteins control eukaryotic transcription • A variety of regulatory proteins interact with DNA and with each other • To turn the transcription of eukaryotic genes on or off

22. 0 Transcription Factors Assist in initiating eukaryotic transcription Enhancers Promoter Gene DNA Activatorproteins Transcriptionfactors Otherproteins RNA polymerase Bendingof DNA Transcription

23. Nucleus Master control gene myoD Other muscle-specific genes DNA OFF OFF Embryonicprecursor cell Determination and differentiation of muscle cells

24. 1 Nucleus Master control gene myoD Other muscle-specific genes DNA OFF OFF Embryonicprecursor cell Determination. Signals from othercells lead to activation of a masterregulatory gene called myoD, andthe cell makes MyoD protein, atranscription factor. The cell, nowcalled a myoblast, is irreversiblycommitted to becoming a skeletalmuscle cell. OFF mRNA MyoD protein(transcriptionfactor) Myoblast (determined) Determination and differentiation of muscle cells

25. 1 2 Nucleus Master control gene myoD Other muscle-specific genes DNA OFF OFF Embryonicprecursor cell Determination. Signals from othercells lead to activation of a masterregulatory gene called myoD, andthe cell makes MyoD protein, atranscription factor. The cell, nowcalled a myoblast, is irreversiblycommitted to becoming a skeletalmuscle cell. OFF mRNA MyoD protein(transcriptionfactor) Myoblast (determined) Differentiation. MyoD protein stimulatesthe myoD gene further, and activatesgenes encoding other muscle-specifictranscription factors, which in turn activate genes for muscle proteins. MyoD also turns on genes that block the cell cycle, thus stopping cell division. The nondividing myoblasts fuse to become mature multinucleate muscle cells, alsocalled muscle fibers. mRNA mRNA mRNA mRNA Myosin, othermuscle proteins,and cell-cycleblocking proteins MyoD Anothertranscriptionfactor Muscle cell(fully differentiated) Determination and differentiation of muscle cells

26. Cytoplasmic Determinants and Cell-Cell Signals in Cell Differentiation • Cytoplasmic determinants in the cytoplasm of the unfertilized egg • Regulate the expression of genes in the zygote that affect the developmental fate of embryonic cells Molecules of another cyto- plasmic deter- minant Sperm Unfertilized egg cell Sperm Molecules of a a cytoplasmic determinant Fertilization Nucleus Zygote (fertilized egg) Mitotic cell division Two-celled embryo

28. (b) Induction by nearby cells. The cells at the bottom of the early embryo depicted here are releasing chemicals that signal nearby cells to change their gene expression. Induction • Signal molecules from embryonic cells cause transcriptional changes in nearby target cells Early embryo (32 cells) Signal transduction pathway NUCLEUS Signal receptor Signal molecule (inducer)

30. Pattern Formation • Pattern formation in animals and plants results from similar genetic and cellular mechanisms • Pattern formation • Is the development of a spatial organization of tissues and organs • Occurs continually in plants • Is mostly limited to embryos and juveniles in animals

31. Cell Positioning • Positional information • Consists of molecular cues that control pattern formation • Tells a cell its location relative to the body’s axes and to other cells

32. Eye Antenna Leg SEM 50 Head of a developmental mutant Head of a normal fruit fly 0 THE GENETIC CONTROL OF EMBRYONIC DEVELOPMENT Cascades of gene expression and cell-to-cell signaling direct the development of an animal • Early understanding of the relationship between gene expression and embryonic development • Came from studies of mutants of the fruit fly Drosophila melanogaster

33. Fly chromosome Mouse chromosomes Fruit fly embryo (10 hours) Mouse embryo (12 days) Adult fruit fly Adult mouse 0 Key Developmental Genes are Very Ancient • Homeotic genes contain nucleotide sequences, called homeoboxes • That are very similar in many kinds of organisms

34. Follicle cell Nucleus Egg cell developing within ovarian follicle Egg cell Nurse cell Fertilization Laying of egg Fertilized egg Egg shell Nucleus Embryo Multinucleate single cell Early blastoderm Plasma membrane formation Yolk Late blastoderm Cells of embryo Body segments Segmented embryo 0.1 mm Hatching Larval stages (3) Pupa Metamorphosis Head Abdomen Thorax Adult fly 0.5 mm Dorsal Anterior Posterior BODY AXES Figure 21.12 Ventral • Key developmental events in the life cycle of Drosophila

36. Tail Head T1 A8 T2 A7 T3 A6 A1 A5 A2 A4 A3 Wild-type larva Tail Tail A8 A8 A7 A6 A7 Mutant larva (bicoid) (a) Drosophila larvae with wild-type and bicoid mutant phenotypes. A mutation in the mother’s bicoid gene leads to tail structures at both ends (bottom larva). The numbers refer to the thoracic and abdominal segments that are present. Bicoid Mutation

37. Hierarchy of Gene Activity in Early Drosophila Development Maternal effect genes (egg-polarity genes) Gap genes Segmentation genes of the embryo Pair-rule genes Segment polarity genes Homeotic genes of the embryo Other genes of the embryo Summary of Gene Activity During Drosophila Development

38. C. elegans: The Role of Cell Signaling The complete cell lineage Of each cell in the nematode roundworm C. elegans is known Zygote 0 First cell division Germ line (future gametes) Outer skin, nervous system Musculature, gonads Nervous system, outer skin, mus- culature Time after fertilization (hours) Musculature 10 Hatching Intestine Intestine Eggs Vulva ANTERIOR POSTERIOR 1.2 mm Figure 21.15

39. 2 Posterior 1 Anterior Signal protein 4 3 Receptor EMBRYO 3 4 Signal Anterior daughter cell of 3 Posterior daughter cell of 3 Will go on to form muscle and gonads Will go on to form adult intestine (a) Induction • As early as the four-cell stage in C. elegans • Cell signaling helps direct daughter cells down the appropriate pathways, a process called induction Figure 21.16a

40. Epidermis Signal protein Gonad Anchor cell Vulval precursor cells Outer vulva ADULT Inner vulva Epidermis Figure 21.16b Induction • also critical later in nematode development • As the embryo passes through three larval stages prior to becoming an adult

41. 2 µm Figure 21.17 Programmed Cell Death (Apoptosis) • In apoptosis • Cell signaling is involved in programmed cell death

42. Interdigital tissue 1 mm Figure 21.19 • In vertebrates • Apoptosis is essential for normal morphogenesis of hands and feet in humans and paws in other animals

43. Plant Development: Cell Signaling and Transcriptional Regulation • Thanks to DNA technology and clues from animal research • Plant research is now progressing rapidly

44. Mechanisms of Plant Development • In general, cell lineage • Is much less important for pattern formation in plants than in animals • The embryonic development of most plants • Occurs inside the seed

45. Carpel Stamen Petal L1 L2 Cell layers L3 Sepal Floral meristem Anatomy of a flower Tomato flower Figure 21.20 Pattern Formation in Flowers • Floral meristems • Contain three cell types that affect flower development

46. Wild type Mutant Figure 21.22 Organ Identity Genes • Organ identity genes • Determine the type of structure that will grow from a meristem • Are analogous to homeotic genes in animals