Chapter 18 Lecture. Concepts of Genetics. Tenth Edition. Developmental Genetics

Transcription

1 Chapter 18 Lecture Concepts of Genetics Tenth Edition Developmental Genetics

2 Chapter Contents 18.1 Differentiated States Develop from Coordinated Programs of Gene Expression 18.2 Evolutionary Conservation of Developmental Mechanisms Can Be Studied Using Model Organisms 18.3 Genetic Analysis of Embryonic Development in Drosophila Reveals How the Animal Body Axis Is Specified 18.4 Zygotic Genes Program Segment Formation in Drosophila 2

3 Chapter Contents 18.5 Homeotic Selector Genes Specify Parts of the Adult Body 18.6 Plants Have Evolved Developmental Systems That Parallel Those of Animals 18.7 Cell-Cell Interactions in Development Are Modeled in C. elegans 18.8 Programmed Cell Death Is Required for Normal Development 3

4 18.1 Differentiated States Develop from Coordinated Programs of Gene Expression 4

5 Section 18.1 Animal genomes contain tens of thousands of genes, but only a fraction of them control the developmental process Development is the attainment of a differentiated state by all cells of an organism 5

6 Section 18.1 According to the variable gene activity hypothesis, differentiation is accomplished by activating and inactivating genes at different times and in different cell types 6

7 18.2 Evolutionary Conservation of Developmental Mechanisms Can Be Studied Using Model Organisms 7

8 Section 18.2 Genetic analysis of development in a wide range of organisms has demonstrated that there are only a small number of developmental mechanisms and signaling systems used in all multicellular organisms Different patterns of expression are controlled by expression in a single cluster of genes called homeotic genes 8

9 Section 18.2 Evolutionary mechanisms for differential development of organisms include mutation gene duplication and divergence the assignment of new functions to old genes the recruitment of genes to new developmental pathways 9

10 Section 18.2 The processes covered in development are how the adult body plan of animals is laid down in the embryo the program of gene expression that turns undifferentiated cells into differentiated cells the role of cell-cell communication in development 10

11 Section 18.2 The primary model organisms used for the study of development are yeast Drosophila C. elegans zebrafish mice Arabidopsis 11

12 18.3 Genetic Analysis of Embryonic Development in Drosophila Reveals How the Animal Body Axis Is Specified 12

13 Section 18.3 Drosophila development, which takes ten days, has five distinct phases of development before the adult stage embryo three larval stages the pupal stage 13

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15 Section 18.3 Internally, the cytoplasm of the fertilized egg is organized into a series of maternally constructed molecular gradients that play key roles in determining the developmental fates of nuclei located in specific regions of the embryo 15

16 Section 18.3 Immediately after fertilization, the zygote nucleus undergoes a number of divisions without cytokinesis These nuclei arrange themselves around the periphery of the egg into cytoplasm containing localized gradients of maternally derived mrna transcripts and proteins Nuclei become enclosed in cells and form cells 16

17 Section 18.3 Segmentation is determined early in development, and within segments cells first become destined to form either the anterior or posterior compartment of the segment Cells forming the posterior pole become germ cells The adult structures form from each segment of the embryo 17

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19 Section 18.3 Genes controlling embryonic development are either maternal-effect genes: mrnas in the egg from the mother zygotic genes: Two copies: One from mom, One from dad, often regulated by the maternal effect genes 19

20 Section 18.3 Products of maternal-effect genes (mrna and proteins) are deposited in the egg cytoplasm Many of these products are distributed in a gradient or concentrated in specific regions of the cell Maternal-effect genes encode transcription factors and proteins that regulate gene expression, the products of which activate or repress expression of the zygotic genome 20

21 Section 18.3 Zygotic genes are transcribed in the nuclei of the developing embryo They are transcribed in specific regions in response to the distribution of maternal-effect proteins 21

22 Section 18.3 The position information laid down by gradients of maternal-effect gene products along the anterior-posterior axis of the embryo regulates expression of the segmentation genes (gap, pair-rule, and segment polarity genes) the homeotic genes that specify the fate of each segment 22

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24 Section 18.3 Most maternal-effect gene products placed in the egg during oogenesis are activated immediately after fertilization. This helps establish the anterior-posterior axis of the embryo Maternal-effect gene products encode transcription factors that activate transcription of the gap gene, whose expression divides the embryo into the head, thorax and abdominal regions of the adult 24

25 Section 18.3 Gap proteins act as transcription factors that activate pair-rule genes whose products divide the embryo into smaller regions about two segments wide Anterior and posterior regions The action of the maternal and segmentation genes is defined by the action of the homeotic (Hox) genes 25

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27 18.4 Zygotic Genes Program Segment Formation in Drosophila 27

28 Section 18.4 The sequential expression of three subsets of segmentation genes divides the embryo into a series of segments along its anterior-posterior axis Over 20 segmentation genes have been identified and are classified as gap, pair-rule, or segment polarity genes 28

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30 Section 18.4 Gap gene mutations produce large gaps in the embryo s segmentation pattern Transcription of gap genes divides the embryo into head, thorax, and abdomen 30

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32 Section 18.4 Within these regions, specific patterns of gene expression specify both the type of segment that will form and the proper order of segments in the body of the larva, pupa, and adult Gap genes control the transcription of pair-rule genes 32

33 Section 18.4 Pair-rule genes are expressed as series of seven narrow bands or stripes that extend around the circumference of the embryo Expression of this gene set first establishes the boundaries of segments, then establishes the developmental fate of the cells within each segment by controlling expression of segment polarity genes At least eight pair-rule genes act to divide the embryo into a series of stripes that overlap 33

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36 Section 18.4 Expression of segment polarity genes is controlled by transcription factors encoded by pair-rule genes Segment polarity genes become active in a single band of cells that extends around the embryo s circumference to divide the embryo into 14 segments 36

37 Section 18.4 The human disorder cleidocranial dysplasia (CCD) is the result of a mutation in the human CBFA gene, the homolog of runt (one of pair-rule genes in Drosophila) It is characterized by numerous skeletal defects 37

38 Section 18.4 Mice with one mutant copy of the runt homolog gene have skeletal abnormalities as seen with humans Those with two mutant copies have complete absence of bone formation, with skeletons containing only cartilage The runt gene is important in controlling the initiation of bone formation 38

39 18.5 Homeotic Selector Genes Specify Parts of the Adult Body 39

40 Section 18.5 The homeotic genes are activated as targets of the zygotic genes and determine which adult structures will be formed by each body segment In homeotic mutants, the structure formed by one segment is transformed into that formed by another segment 40

41 Section 18.5 The Drosophila genome contains two clusters of homeotic selector (Hox) genes on chromosome 3 that encode transcription factors 41

42 Section 18.5 The Antennapedia complex contains five genes that specify structures in the head and the first two thoracic segments The second cluster, the bithorax (BX-C) complex, contains three genes that specify structures in the second thoracic segment and the entire third thoracic segment and the abdominal segment 42

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44 Section 18.5 Hox genes contain a 180-bp domain known as a homeobox The homeobox encodes a DNA-binding sequence of 60 amino acids known as a homeodomain Expression of the Hox genes is colinear, with anterior-toposterior organization in the embryo 44

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46 Section 18.5 In summary 1. Gap genes are activated to subdivide the embryo into broad bands 2. Gap genes activate pair-rule genes that divide the embryo into segments. 3. Segment polarity genes divide each segment into anterior-posterior axes, which are then given identity by the Hox genes 46

47 Section 18.5 Hox genes are in the genomes of all animals, playing a fundamental role in shaping the body and its appendages In vertebrates, these genes control development along the anterior-posterior axis and the formation of appendages Humans and most vertebrates have four clusters of Hox genes (HOXA, HOXB, HOXC, and HOXD) containing 39 genes A cluster of two to four Hox genes is involved in forming specific structures These genes control the pattern of structures along the anterior-posterior axis 47

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49 Patterns of Hox gene expression control the formation of structures along the anterior-posterior axis of bilaterally symmetrical animals in a species-specific manner 49

50 Section 18.5 Homeotic mutations in individual vertebrate Hox genes do not produce complete transformations as in Drosophila In human development, several inherited limb malformations are caused by mutations in HOXD genes Synpolydactyly (SPD), caused by mutations in HOXD 13, is characterized by extra fingers and toes and bone abnormalities in the hands and feet 50

51 18.6 Plants Have Evolved Developmental Systems That Parallel Those of Animals 51

52 Section 18.6 Plants and animals diverged from a common unicellular ancestor 1.6 billion years ago. Development patterns evolved independently in plants and animals Pattern formations in plants have been studied using Arabidopsis thaliana Floral meristem, a group of undifferentiated cells, gives rise to flowers Each flower consists of four organs that develop from concentric rings of cells within the meristem sepals, petals, stamens, carpel 52

53 Section 18.6 Three classes of floral homeotic genes control development of these organs Sepal development is controlled by Class A genes alone Petal development is controlled by Class A and Class B genes expressed together Stamen development is controlled by Class B and Class C genes Carpel development is controlled by Class C genes alone 53

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55 Section 18.6 Mutations in homeotic genes in plants cause organs to develop in abnormal locations, as in Drosophila In APETALA2 mutants, the order is carpel, stamen, stamen, and carpel instead of sepal, petal, stamen and carpel Various other mutants result in deviations of the original order of organs 55

56 Section 18.6 Although development in both plants and Drosophila is regulated by a set of master regulatory genes that encode transcription factors, the homeotic genes of Arabidopsis do not share sequence homology with the Drosophila Hox genes Arabidopsis homeotic genes belong to a family of transcription factors called MADS-box proteins In both plants and animals, the action of transcription factors depends on changes in chromatin structure making genes available for expression Action of the floral homeotic genes is controlled by the CURLY LEAF gene. CURLY LEAF and Polycomb Drosophila gene alter chromatin configuration and shut off gene expression 56

57 18.7 Cell-Cell Interactions in Development Are Modeled in C. elegans 57

58 Section 18.7 Cell-cell interactions influence the transcriptional programs and developmental fate of neighboring cells during embryonic development Signaling systems in early embryonic development act both independently and in coordinated networks to send and receive developmental signals that elicit specific transcriptional responses 58

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60 Section 18.7 The Notch signaling pathway is a short-range system that works through direct cell-cell contact to control the developmental fate of interacting cells The Notch gene encodes a signal receptor embedded in the plasma membrane The signal is another transmembrane protein encoded by the Delta gene that works between adjacent cells 60

61 Section 18.7 One of the main roles of the Notch signal system is specifying the fate of equivalent cells in a population where the interaction involves two neighboring cells C. elegans has well-understood genetics and a completed genome sequence Adults are formed from 959 somatic cells, for each of which the developmental lineage from fertilized egg to adult has been mapped 61

62 A truncated cell lineage chart for C. elegans, showing early divisions and the tissues and organs formed from these lineages. The first division of the zygote creates two new cells, AB and P1. During embryogenesis, cell divisions will produce the 959 somatic cells of the adult hermaphrodite worm

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64 Cell lineage determination in C. elegans vulva formation. A signal from the anchor cell in the form of LIN-3 protein is received by three precursor vulval cells (Pn.p cells). The cell closest to the anchor cell becomes the primary vulval precursor cell, and adjacent cells become secondary precursor cells. The primary cell produces a signal that activates the lin-12 gene in secondary cells, preventing them from becoming primary cells. Flanking precursor cells, which receive no signal from the anchor cell, become skin (hypodermis) cells, instead of vulval cells

65 Section 18.7 Vulval development involves three rounds of cell-cell interactions that transmit or receive signals from other cells Cell-cell interactions act in a spatial and temporal cascade to specify the developmental fates of individual cells 65

66 18.8 Programmed Cell Death Is Required for Normal Development 66

67 Section 18.8 Programmed cell death is genetically controlled and helps shape tissues and organs The formation of digits in vertebrate limbs requires the death of the cells between the digits in a process called apoptosis Mutation analysis shows that programmed cell death occurs in cells in different lineages using the same genetic pathway 67

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