1. Genes, Development, and Evolution 14

2. BIG IDEA #1 The Process of Evolution Drives the Diversity & Unity of Life

3. Concept 14.1 Development Involves Distinct but Overlapping Processes Development—the process by which a multicellular organism undergoes a series of changes, taking on forms that characterize its life cycle. After the egg is fertilized, it is called a zygote. In its earliest stages, a plant or animal is called an embryo. The embryo can be protected in a seed, an egg shell, or a uterus.

4. Figure 14.1 Development (Part 2)

5. Figure 14.1 Development (Part 1)Part

6. Concept 14.2 Changes in Gene Expression Underlie Cell Differentiation in Development Polarity—having a “top” and a “bottom” may develop in the embryo. The animal pole is the top, the vegetal pole is the bottom. Polarity can lead to determination of cell fates early in development.

7. Concept 14.2 Changes in Gene Expression Underlie Cell Differentiation in Development Polarity was demonstrated using sea urchin embryos. If an eight-cell embryo is cut vertically, it develops into two normal but small embryos. If the eight-cell embryo is cut horizontally, the bottom develops into a small embryo, the top does not develop.

8. In-Text Art, Ch. 14, p. 270

9. Figure 14.8 The Concept of Cytoplasmic Segregation

10. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis The fruit fly Drosophila melanogaster has a body made of different segments. The head, thorax, and abdomen are each made of several segments. 24 hours after fertilization a larva appears, with recognizable segments that look similar. The fates of the cells to become different adult segments are already determined.

11. In-Text Art, Ch. 14, p. 276 (2)

12. In-Text Art, Ch. 14, p. 276 (1)

13. Concept 14.2 Changes in Gene Expression Underlie Cell Differentiation in Development Model of cytoplasmic segregation states that cytoplasmic determinants are distributed unequally in the egg. The cytoskeleton contributes to distribution of cytoplasmic determinants: Microtubules and microfilaments have polarity. Cytoskeletal elements can bind certain proteins.

14. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Cytokinesis does not occur in the early Drosophila mitoses after fertilization. The embryo until then is multinucleate, allowing for easy diffusion of morphogens. Experimental genetics were used: Developmental mutant strains were identified. Genes for mutations were identified. Transgenic flies were produced to confirm the developmental pathway.

15. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Several types of genes are expressed sequentially to define the segments: Maternal effect genes set up anterior–posterior and dorsal–ventral axes in the egg. Segmentation genes determine boundaries and polarity. Hox genes determine what organ will be made at a given location.

16. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Maternal effect genes produce cytoplasmic determinants in unequal distributions in the egg. Two genes—bicoid and nanos—determine the anterior–posterior axis. Their mRNAs diffuse to the anterior end of the egg. Bicoid protein diffuses away from the anterior end, establishing a gradient.

17. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis At sufficient concentration, bicoid stimulates transcription of the Hunchback gene. A gradient of that protein establishes the head. Nanos mRNA is transported to the posterior end. Nanos protein inhibits translation of Hunchback. After the anterior and posterior ends are established, the next step is determination of segment number and locations.

18. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Segmentation genes determine properties of the larval segments. Three classes of genes act in sequence: Gap genes organize broad areas along the axis Pair rule genes divide embryo into units of two segments each Segment polarity genes determine boundaries and anterior–posterior organization in individual segments

19. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Hox genes are expressed in different combinations along the length of the embryo. They determine cell fates within each segment and direct cells to become certain structures, such as eyes or wings. Hox genes are homeotic genes that are shared by all animals.

20. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Clues to hox gene function came from homeotic mutants. Antennapedia mutation—legs grow in place of antennae. Bithorax mutation—an extra pair of wings grow.

21. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Antennapedia and bithorax have a common 180-bp sequence—the homeobox, that encodes a 60- amino acid sequence called the homeodomain. The homeodomain binds to a specific DNA sequence in promoters of target genes.

22. Figure 14.13 A Gene Cascade Controls Pattern Formation in the Drosophila Embryo

23. Concept 14.4 Gene Expression Pathways Underlie the Evolution of Development Through hybridization, sequencing, and comparative genomics, it is known that diverse animals share molecular pathways for gene expression in development. Fruit fly genes have mouse and human orthologs for developmental genes. These genes are arranged on the chromosome in the same order as they are expressed along the anterior–posterior axis of their embryos—the positional information has been conserved.

24. Concept 14.4 Gene Expression Pathways Underlie the Evolution of Development Principles of evo-devo: Many groups of animals and plants share similar molecular mechanisms for morphogenesis and pattern formation. The molecular pathways that determine different developmental processes operate independently from one another— called modularity.

25. Concept 14.4 Gene Expression Pathways Underlie the Evolution of Development The homeobox is also present in many genes in other organisms, showing a similarity in the molecular events of morphogenesis. Evolutionary developmental biology (evo-devo) is the study of evolution and developmental processes.

26. Concept 14.4 Gene Expression Pathways Underlie the Evolution of Development In an embryo, genetic switches integrate positional information and play a key role in making different modules develop differently. Genetic switches control the activity of Hox genes by activating each Hox gene in different zones of the body. The same switch can have different effects on target genes in different species, important in evolution.

27. Concept 14.5 Developmental Genes Contribute to Species Evolution but Also Pose Constraints Genetic switches that determine where and when genes are expressed underlie both development and the evolution of differences among species. Among arthropods, the Hox gene Ubx produces different effects. In centipedes, Ubx protein activates the Dll gene to promote the formation of legs. In insects, a change in the Ubx gene results in a protein that represses Dll expression, so leg formation is inhibited.

28. Figure 14.15 Regulatory Genes Show Similar Expression Patterns

29. Figure 14.16 Segments Differentiate under Control of Genetic Switches (Part 2)

30. Figure 14.16 Segments Differentiate under Control of Genetic Switches

31. Concept 14.1 Development Involves Distinct but Overlapping Processes As zygote develops, the cell fate of each undifferentiated cell drives it to become part of a particular type of tissue. ExperimentsExperiments in which specific cells of an early embryo are grafted to new positions on another embryo show that cell fate is determined during development.

32. Figure 14.2 A Cell’s Fate Is Determined in the EmbryoEmbryo

33. Concept 14.1 Development Involves Distinct but Overlapping Processes Four processes of development: Determination sets the fate of the cell Differentiation is the process by which different types of cells arise Morphogenesis is the organization and spatial distribution of differentiated cells Growth is an increase in body size by cell division and cell expansion

34. Concept 14.2 Changes in Gene Expression Underlie Cell Differentiation in Development Two ways to make a cell transcribe different genes: Asymmetrical factors that are unequally distributed in the cytoplasm may end up in different amounts in progeny cells Differential exposure of cells to an inducer

35. Concept 14.2 Changes in Gene Expression Underlie Cell Differentiation in Development Induction refers to the signaling events in a developing embryo. Cells influence one another’s developmental fate via chemical signals and signal transduction mechanisms. Exposure to different amounts of inductive signals can lead to differences in gene expression.

36. Concept 14.2 Changes in Gene Expression Underlie Cell Differentiation in Development Induction involves the activation or inactivation of specific genes through signal transduction cascades in the responding cells. Example from nematode development: Much of development is controlled by the molecular switches that allow a cell to proceed down one of two alternative tracks.

37. Concept 14.2 Changes in Gene Expression Underlie Cell Differentiation in Development In C. elegans, the cell divisions from the fertilized egg to the 959 adult cells can be followed. Nematodes are hermaphroditic and contain male and female reproductive organs. Eggs are laid through a pore, the vulva. During development, a single anchor cell induces the vulva to form from six cells on the ventral surface of the worm.

38. Concept 14.2 Changes in Gene Expression Underlie Cell Differentiation in Development LIN-3, a protein secreted by the anchor cell acts as the primary inducer. The primary precursor cell that received the most LIN-3 then secretes a secondary inducer (lateral signal) that acts on its neighbors. The gene expression patterns triggered by these molecular switches determine cell fates.

39. Figure 14.9 Induction during Vulval Development in Caenorhabditis elegans

40. Figure 14.10 The Concept of Embryonic Induction

41. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Programmed cell death— apoptosis—is also important. Many cells and structures form and then disappear during development. Sequential expression of two genes called ced-3 and ced-4 (for cell death) are essential for apoptosis. Their expression in the human embryo guides development of fingers and toes. Worksheet 201 Positive and negative control of apoptosis

42. Concept 14.4 Gene Expression Pathways Underlie the Evolution of Development Webbed feet in ducks result from an altered spatial expression pattern of a developmental gene. Duck and chicken embryos both have webbing, and both express BMP4, a protein that instructs cells in the webbing to undergo apoptosis.

43. Concept 14.4 Gene Expression Pathways Underlie the Evolution of Development In ducks, a gene called Gremlin, which encodes a BMP inhibitor protein, is expressed in webbing cells. In chickens, Gremlin is not expressed, and BMP4 signals apoptosis of the webbing cells. Experimental application of Gremlin to chicken feet results in a webbed foot.

44. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Flowers are composed of four organ types (sepals, petals, stamens, carpels) arranged around a central axis in whorls. In Arabidopsis thaliana, flowers develop from a meristem at the growing point on the stem. The identity of each whorl is determined by organ identity genes.

45. Figure 14.11 Gene Expression and Morphogenesis in Arabidopsis Flowers

46. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Fate of a cell is determined by where the cell is. Positional information comes in the form an inducer, a morphogen, which diffuses from one group of cells to another, setting up a concentration gradient. directly affect target cells Different concentrations of the morphogen result in different effects

47. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis The “French flag model” explains morphogens and can be applied to differentiation of the vulva in C. elegans and to development of vertebrate limbs. Vertebrate limbs develop from paddle-shaped limb buds—cells must receive positional information. Cells of the zone of polarizing activity (ZPA) secrete a morphogen called Sonic hedgehog (Shh). It forms a gradient that determines the posterior– anterior axis.

48. Figure 14.12 The French Flag Model

49. Concept 14.5 Developmental Genes Contribute to Species Evolution but Also Pose Constraints Evolution of form has not been a result of radically new genes but has resulted from modifications of existing genes. Developmental genes constrain evolution in two ways: Nearly all evolutionary innovations are modifications of existing structures. Genes that control development are highly conserved.

50. Figure 14.19 A Mutation in a Hox Gene Changed the Number of Legs in Insects

51. Concept 14.5 Developmental Genes Contribute to Species Evolution but Also Pose Constraints Wings arose as modifications of existing structures. In vertebrates, wings are modified limbs. Organisms also lose structures. Ancestors of snakes lost their forelimbs as a result of changes in expression of Hox genes. Then hindlimbs were lost by the loss of expression of the Sonic hedgehog gene in limb bud tissue.

52. Figure 14.20 Wings Evolved Three Times in Vertebrates

53. Concept 14.5 Developmental Genes Contribute to Species Evolution but Also Pose Constraints Many developmental genes exist in similar form across a wide range of species. Highly conserved developmental genes make it likely that similar traits will evolve repeatedly: Parallel phenotypic evolution. Example: Three-spined sticklebacks (Gasterosteus aculeatus)

54. Concept 14.5 Developmental Genes Contribute to Species Evolution but Also Pose Constraints Marine populations of sticklebacks return to freshwater to breed. Freshwater populations never go into saltwater environments. Freshwater populations have arisen many times from adjacent marine populations. Marine populations have pelvic spines and bony plates that protect them from predation. These are greatly reduced in freshwater populations. One gene, Pitx1, is not expressed in freshwater sticklebacks, and spines do not develop. This same gene has evolved to produce similar phenotypic changes in several independent populations.

55. Figure 14.21 Parallel Phenotypic Evolution in Sticklebacks

56. Stem Cells Stem cells are valuable because they are not differentiated and can develop into several kinds of cells. When fat stem cells are injected into a damaged area they respond to the environment of that tissue. Inducers in the environment determine the products of cell differentiation.

57. Figure 14.22 Differentiation Potential of Stem Cells from Fat

58. Concept 14.1 Development Involves Distinct but Overlapping Processes Determination is influenced by changes in gene expression as well as the external environment. Determination is a commitment; the final realization of that commitment is differentiation. Differentiation is the actual changes in biochemistry, structure, and function that result in cells of different types.

59. Concept 14.1 Development Involves Distinct but Overlapping Processes Determination is followed by differentiation—under certain conditions a cell can become undetermined again. It may become totipotent—able to become any type of cell. Plant cells are usually totipotent but can be induced to dedifferentiate into masses of calli, which can be cultured into clones. Genomic equivalence—all cells in a plant have the complete genome for that plant.

60. Concept 14.1 Development Involves Distinct but Overlapping Processes Pluripotent cells in the blastocyst embryonic stage retain the ability to form all of the cells in the body. In mice, embryonic stem cells (ESCs) can be removed from the blastocyst and grown in laboratory culture almost indefinitely. ESCs in the laboratory can also be induced to differentiate by specific signals, such as Vitamin A to form neurons or growth factors to form blood cells.

61. Figure 14.6 Two Ways to Obtain Pluripotent Stem Cells

62. Concept 14.1 Development Involves Distinct but Overlapping Processes Induced pluripotent stem cells (iPS cells) can be made from skin cells: Microarrays are used to find genes uniquely expressed at high levels in ESCs. The genes are inserted into a vector for genetic transformation of skin cells—skin cells express added genes at high levels. The transformed cells become iPS cells and can be induced to differentiate into many tissues.

63. Concept 14.1 Development Involves Distinct but Overlapping Processes Stem cells in some mammalian tissues are multipotent—they produce cells that differentiate into a few cell types. Hematopoietic stem cells produce red and white blood cells. Mesenchymal stem cells produce bone and connective tissue cells.

64. Concept 14.1 Development Involves Distinct but Overlapping Processes In animals, nuclear transfer experiments have shown that genetic material from a cell can be used to create cloned animals. The nucleus is removed from an unfertilized egg, forming an enucleated egg. A donor nucleus from a differentiated cell is then injected into the enucleated egg. The egg divides and develops into a clone of the nuclear donor.

65. Figure 14.4 Cloning a Mammal (Part 1)

66. Concept 14.1 Development Involves Distinct but Overlapping Processes As in plants, no genetic information is lost as the cell passes through developmental stages — genomic equivalence. Practical applications for cloning: Expansion of numbers of valuable animals Preservation of endangered species Preservation of pets

67. Concept 14.1 Development Involves Distinct but Overlapping Processes Therapies that kill cancer cells can also kill other rapidly dividing cells such as bone marrow stem cells. The stem cells are removed and stored during the therapy, and then returned to the bone marrow. The stored stem cells retain their ability to differentiate.

68. Concept 14.1 Development Involves Distinct but Overlapping Processes ESC cultures may be sources of differentiated cells to repair damaged tissues, as in diabetes or Parkinson’s disease. ESCs can be harvested from human embryos conceived by in vitro fertilization, with consent of the donors. However: Some people object to the destruction of human embryos for this purpose The stem cells could provoke an immune response in a recipient

69. Concept 14.2 Changes in Gene Expression Underlie Cell Differentiation in Development In the vertebrate embryo, muscle precursor cells come from a tissue layer called the mesoderm. When these cells commit to becoming muscle cells, they stop dividing—in many parts of the embryo, cell division and cell differentiation are mutually exclusive.

70. Concept 14.2 Changes in Gene Expression Underlie Cell Differentiation in Development Cell signaling activates the gene for a transcription factor called MyoD. MyoD activates the gene for p21, an inhibitor of cyclin-dependent kinases that normally stimulate the cell cycle at G1. The cell cycle stops so that differentiation can begin.

71. Figure 14.7 Transcription and Differentiation in the Formation of Muscle Cells