1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Chapter 21 The Genetic Basis of Development

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Overview: From Single Cell to Multicellular Organism Genetic analysis and DNA technology have revolutionized the study of development Researchers use mutations to deduce developmental pathways They apply concepts and tools of molecular genetics to the study of developmental biology

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

4. When the primary research goal is to understand broad biological principles, the organism chosen for study is called a model organism Researchers select model organisms that are representative of a larger group – Have readily observable embryos – Short generation time – Small genomes – Knowledge about organisms genes available

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

9. Concept 21.1: Embryonic development involves cell division, cell differentiation, and morphogenesis In embryonic development of most organisms, a single-celled zygote gives rise to cells of many different types, each with a different structure and corresponding function Development involves three processes: cell division, cell differentiation, and morphogenesis (“creation of form”)

10. LE 21-3 Fertilized egg of a frogTadpole hatching from egg

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 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

12. LE 21-4 Animal development Zygote (fertilized egg) Eight cellsBlastula (cross section) Gastrula (cross section) Adult animal (sea star) Cell movement Gut Cell division Morphogenesis Observable cell differentiation Seed leaves Shoot apical meristem Root apical meristem Plant Embryo inside seed Two cells Zygote (fertilized egg) Plant development

13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Development in animals, but not in plants, involves cell movement which transforms embryo into its form. Development in plants, but not animals, morphogenesis and growth continue throughout life of plant – Apical meristems are the perpetually embryonic regions in tips of shoots and roots that are responsible for continued growth and formation of new structures

14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 21.2: Different cell types result from differential gene expression in cells with the same DNA Differences between cells in a multicellular organism come almost entirely from gene expression, not differences in the cells’ genomes These differences arise during development, as regulatory mechanisms turn genes off and on

15. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Evidence for Genomic Equivalence Many experiments support the conclusion that nearly all cells of an organism have genomic equivalence (the same genes) In other words, all somatic cells have identical genomes regardless of their type, or state of differentiation. Different cell types express different genes (differential gene expression) A key question that emerges is whether genes are irreversibly inactivated during differentiation

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Totipotency in Plants One experimental approach for testing genomic equivalence is to see whether a differentiated cell can generate a whole organism A totipotent cell is one that can generate a complete new organism A pluripotent cell can give rise to some but not all cell types Cloning is using one or more somatic cells from a multicellular organism to make a genetically identical individual

17. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Nuclear Transplantation in Animals Nuclear transplantation, is a cloning method involving the transfer of a nucleus from a differentiated cell into an enucleated (nucleus removed) egg cell or zygote Experiments with frog embryos have shown that a transplanted nucleus can often support normal development of the egg

18. LE 21-6 Frog embryoFrog egg cellFrog tadpole UV Less differ- entiated cell Donor nucleus trans- planted Enucleated egg cell Most develop into tadpoles <2% develop into tadpoles Donor nucleus trans- planted Fully differ- entiated (intestinal) cell

19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Reproductive Cloning of Mammals In 1997, Scottish researchers announced the birth of Dolly, a lamb cloned from an adult sheep by nuclear transplantation from a differentiated mammary cell (a differentiated adult cell could be dedifferentiated) Dolly’s premature death in 2003, as well as her arthritis, led to speculation that her cells were “older” than those of a normal sheep, possibly reflecting incomplete reprogramming of the original transplanted nucleus

20. LE 21-7 Mammary cell donor Egg cell donor Egg cell from ovary Nucleus removed Cells fused Cultured mammary cells are semistarved, arresting the cell cycle and causing dedifferentiation Nucleus from mammary cell Early embryo Grown in culture Implanted in uterus of a third sheep Surrogate mother Embryonic development Lamb (“Dolly”) genetically identical to mammary cell donor

21. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Since 1997, cloning has been demonstrated in many mammals, including mice, cats, cows, horses, and pigs “Copy Cat” was the first cat cloned

22. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

23. The Stem Cells of Animals A stem cell is a relatively unspecialized cell that can reproduce itself indefinitely and differentiate into specialized cells of one or more types Stem cells isolated from early embryos at the blastocyst stage are called embryonic stem cells The adult body also has stem cells, which replace nonreproducing specialized cells Embryonic stem cells are totipotent, able to differentiate into all cell types Adult stem cells are pluripotent, able to give rise to multiple but not all cell types

24. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings True or false? 1.Stem cell are found in the brain? 2.Stem cells are found in bone marrow? 3.Stem cell DNA lacks introns? 4.Stem cell can reproduce themselves? 5.Stem cells can differentiate

25. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 1.True 2.True 3.False 4.True 5.True

26. LE 21-9 Embryonic stem cellsAdult stem cells Pluripotent cells Totipotent cells Cultured stem cells Different culture conditions Different types of differentiated cells Liver cellsNerve cellsBlood cells

27. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Transcriptional Regulation of Gene Expression During Development Cell determination precedes differentiation and involves expression of genes for tissue-specific proteins In most cases differentiation is controlled at the level of transcription Tissue-specific proteins enable differentiated cells to carry out their specific tasks

28. LE 21-10_1 Nucleus Embryonic precursor cell DNA OFF Master control gene myoDOther muscle-specific genes

29. LE 21-10_2 Nucleus Embryonic precursor cell DNA OFF Master control gene myoDOther muscle-specific genes mRNAOFF Determination Myoblast (determined) MyoD protein (transcription factor)

30. LE 21-10_3 Nucleus Embryonic precursor cell DNA OFF Master control gene myoDOther muscle-specific genes mRNAOFF Determination Myoblast (determined) MyoD protein (transcription factor) Differentiation Muscle cell (fully differentiated) mRNA MyoD mRNA Another transcription factor Myosin, other muscle proteins, and cell-cycle blocking proteins

31. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytoplasmic Determinants and Cell-Cell Signals in Cell Differentiation Maternal substances that influence early development are called cytoplasmic determinants These substances regulate expression of genes that affect the cell’s developmental fate

32. LE 21-11a Sperm Molecules of a cytoplasmic determinant Fertilization Nucleus Molecules of another cytoplasmic determinant Unfertilized egg cell Zygote (fertilized egg) Mitotic cell division Two-celled embryo Cytoplasmic determinants in the egg

33. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The other important source of developmental information is the environment around the cell, especially signals from nearby embryonic cells In the process called induction, signal molecules from embryonic cells cause transcriptional changes in nearby target cells

34. LE 21-11b Early embryo (32 cells) Signal transduction pathway Signal receptor Signal molecule (inducer) NUCLEUS Induction by nearby cells

35. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 21.3: 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 It occurs continually in plants, but it is mostly limited to embryos and juveniles in animals Positional information, the molecular cues that control pattern formation, tells a cell its location relative to the body axes and to neighboring cells

36. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Drosophila Development: A Cascade of Gene Activations Pattern formation has been extensively studied in the fruit fly Drosophila melanogaster Combining anatomical, genetic, and biochemical approaches, researchers have discovered developmental principles common to many other species, including humans

37. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Life Cycle of Drosophila After fertilization, positional information specifies the body segments in Drosophila Positional information triggers the formation of each segment’s characteristic structures Sequential gene expression produces regional differences in the formation of the segments

38. LE 21-12 Egg cell developing within ovarian follicle Follicle cell Nucleus Egg cell Fertilization Nurse cell Fertilized egg Embryo Nucleus Laying of egg Egg shell Multinucleate single cell Early blastoderm Plasma membrane formation Late blastoderm Yolk Body segments Cells of embryo Segmented embryo 0.1 mm Hatching Larval stages (3) Pupa Metamorphosis Adult fly Head Thorax Abdomen 0.5 mm BODY AXES Dorsal Ventral PosteriorAnterior

39. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Genetic Analysis of Early Development: Scientific Inquiry Study of developmental mutants laid the groundwork for understanding the mechanisms of development Mutations that affect segmentation are likely to be embryonic lethals, leading to death at the embryonic or larval stage

40. LE 21-13 Eye Antenna Leg Wild typeMutant

41. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Axis Establishment Maternal effect genes encode for cytoplasmic determinants that initially establish the axes of the body of Drosophila These maternal effect genes are also called egg- polarity genes because they control orientation of the egg and consequently the fly

42. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings One maternal effect gene, the bicoid gene, affects the front half of the body An embryo whose mother has a mutant bicoid gene lacks the front half of its body and has duplicate posterior structures at both ends This phenotype suggests that the product of the mother’s bicoid gene is concentrated at the future anterior end This hypothesis is an example of the gradient hypothesis, in which gradients of substances called morphogens establish an embryo’s axes and other features

43. LE 21-14a Head Tail Wild-type larva Mutant larva (bicoid) Drosophila larvae with wild-type and bicoid mutant phenotypes

44. LE 21-14b Developing egg cell Bicoid mRNA in mature unfertilized egg Nurse cells Egg cell bicoid mRNA Bicoid protein in early embryo Fertilization Translation of bicoid mRNA 100  Anterior end Gradients of bicoid mRNA and Bicoid protein in normal egg and early embryo m

45. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Segmentation Pattern Segmentation genes produce proteins that direct formation of segments after the embryo’s major body axes are formed Positional information is provided by sequential activation of three sets of segmentation genes: gap genes, pair-rule genes, and segment-polarity genes

46. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Identity of Body Parts The anatomical identity of Drosophila segments is set by master regulatory genes called homeotic genes Mutations to homeotic genes produce flies with strange traits, such as legs growing from the head in place of antennae

47. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

48. C. elegans: The Role of Cell Signaling The nematode C. elegans is a very useful model organism for investigating the roles of cell signaling, induction, and programmed cell death in development Researchers know the entire ancestry of every cell of an adult C. elegans—the organism’s complete cell lineage Video: C. elegans Embryo Development (time lapse) Video: C. elegans Embryo Development (time lapse)

49. LE 21-15 Nervous system, outer skin, mus- culature Time after fertilization (hours) Musculature, gonads 0 10 Zygote First cell division Hatching Outer skin, nervous system Intestine Musculature Germ line (future gametes) Intestine EggsVulva ANTERIOR 1.2 mm POSTERIOR

50. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 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

51. LE 21-16a Anterior EMBRYO Posterior Receptor Signal protein 1 2 3 4 4 3 Signal Posterior daughter cell of 3 Anterior daughter cell of 3 Will go on to form muscle and gonads Will go on to form adult intestine Induction of the intestinal precursor cell at the four-cell stage

52. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Programmed Cell Death (Apoptosis) Cell signaling is involved in apoptosis, programmed cell death During apoptosis, a cell shrinks and becomes lobed (called “blebbing”); the nucleus condenses; and the DNA is fragmented

53. LE 21-17 2  m

54. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In C. elegans, a protein in the outer mitochondrial membrane is a master regulator of apoptosis Research on mammals has revealed a prominent role for mitochondria in apoptosis A built-in cell suicide mechanism is essential to development in all animals Removes damaged cells

55. LE 21-18 Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Ced-4Ced-3 Inactive proteins Death signal receptor No death signal Death signal Ced-9 (inactive) Cell forms blebs Active Ced-4 Active Ced-3 Other proteases Nucleases Activation cascade Death signal

56. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The timely activation of apoptosis proteins in some cells functions during normal development and growth in both embryos and adult In vertebrates, apoptosis is part of normal development of the nervous system, operation of the immune system, morphogenesis of hands and feet in humans and paws in other mammals and morphogenesis of gonads.

57. LE 21-19 Interdigital tissue 1 mm