2 Genes and DevelopmentThe genotype determines not only the events that take place in development but also the temporal order in which the events unfoldA key process in development is pattern formation, which means emergence of spatially organized and specialized cells in the embryo from cell division and differentiation of the fertilized eggGenetic analyses of development often make use of mutations that alter developmental patterns
3 Development: Transcriptional Control S. cerevisiae has two mating types denoted a and The specific mating type of a cell is controlled at the level of transcriptionThe alternative mating-type alleles MATa (mating type a) and MAT (mating type ) both express a set of haploid-specific genes, including HO for the HO endonuclease used in mating-type interconversion, and RME1 for a repressor of meiosis-specific genes.
4 Development: Transcriptional Control MATa also expresses a set of a-specific genes and MAT expresses a set of -specific genes.Expression of genes that differ in the mating types includesecretion of a mating peptideproduction of a receptor for the mating peptide secreted by the opposite mating type
5 Development: Transcriptional Control Therefore, when a and cells are in proximity, they prepare each other for mating and undergo fusionIn a cell of mating type a, the MATa region is transcribed and a polypeptide called a1 is produceda1 alone is an inactive regulator, and in the absence of any regulatory signal, asg (a-specific genes) and hsg (haploid-specific genes) are transcribed, but sg (-specific genes ) are not
6 Development: Transcriptional Control In a cell of mating type , the MAT region is transcribed and proteins 1 and 2 are produced: 1 is a positive regulator of the -specific genes, and 2 is a negative regulator of the a-specific genesThe result is that sg and hsg are transcribed, but transcription of asg is turned off.
7 Development: Transcriptional Control In the diploid both MATa and MAT are transcribed, but the only polypeptides produced are a1 and 2The reason is that the a1 and 2 combine to form a negative regulator of the 1 gene in MAT and of the hsg
8 Development: Transcriptional Control The 2 polypeptide acting alone is a negative regulatory protein that turns off asgBecause 1 is not produced, transcription of sg is not turned on
9 Development: Transcriptional Control The overall result is that the sg are not turned on because 1 is absent, the asg are turned off because 2 is present, and the hsg are turned off by the a1/2 complexThis ensures that meiosis can occur (RME1 is turned off) and that mating-type switching ceases (the HO endonuclease is absent).
10 Figure 11.1: Transcriptional regulation of mating type in yeast
11 Caenorhabditis elegans Nematodes are diploid organisms with two sexesIn C. elegans, the two sexes are the hermaphrodite and the maleThe hermaphrodite contains two X chromosomes (XX), produces both functional eggs and functional sperm, and is capable of self-fertilizationThe male produces only sperm and fertilizes the hermaphroditesThere is no Y chromosome, and the male karyotype is XO
12 Caenorhabditis elegans Nematode development is unusual: the pattern of cell division and differentiation is virtually identical from one individual to the nextAs a result each sex shows the same geometry in the number and arrangement of somatic cellsThe hermaphrodite contains exactly 959 somatic cells, and the male contains exactly 1031 somatic cellsThe complete developmental history of each somatic cell is known
13 Genetic Control of Cell Lineages Lineage of a cell is ancestor-descendant relationships among a group of cellsLineage diagram is a sort of cell pedigree that shows each cell division and indicates the terminal differentiated state of each cellCell fate is determined by autonomous development and/or intercellular signaling.Figure 11.3: Hypothetical cell-lineage diagram
14 Gene Regulation in Development Cell fate: developmental outcome of cells within a lineageCell fate is progressively restricted in animal development
15 Gene Regulation in Development Two principle mechanisms progressively restrict cell development:Developmental restriction may be autonomous, which means that it is determined by genetically programmed changes in the cells themselvesCells also may respond to positional information, which means that developmental restrictions are imposed by the position of cells within the embryo.Positional information may be mediated by signaling interactions between neighboring cells or by gradients in concentration of particular molecules.
16 Genes and DevelopmentMany mutations studied in nematodes reveal several general features by which genes control development:The division pattern and fate of a cell are generally affected by more than one geneMost genes that affect development are active in more than one type of cell
17 Genes and DevelopmentComplex lineages often include simpler, genetically determined sublineages within themThe lineage of a cell may be triggered autonomously within the cell itself or by signaling interactions with other cellsRegulation of development is controlled by genes that determine the different sublineages that cells can undergo and the individual steps within each sublineage.
18 Genes and Cell FateGenes that control cell fate can be identified by the unusual property: dominant and recessive mutations have opposite effectsIf alternative alleles of a gene result in opposite cell fates, then the product of the gene must be both necessary and sufficient for expression of the fate
19 Genes and Cell FateRecessive mutations often result from loss of function—the mRNA is not produced or the protein is inactiveDominant mutations often result from gain of function—the gene is overexpressed or is expressed at the wrong time
20 Lineage MutationsIn C. elegans, a relatively small number of genes have dominant and recessive alleles that affect the same cells in opposite waysAmong them is the lin-12 gene, which controls developmental decisions in a number of cellsThe molecular structure of the lin-12 gene product is typical of a transmembrane receptor protein containing regions that span the cell membrane
22 Lineage MutationsCells can determine the fate of other cells through ligands that bind with their transmembrane receptorslin-3 expressed in anchor cell controls the fate of other cells in the development of the vulvaLoss of LIN-3 results in the complete absence of vulval development, whereas overexpression of LIN-3 results in excess vulval induction.LIN-3 is a typical example of an interacting molecule, or ligand, that binds with an EGF-type transmembrane receptor
23 Figure 11.7: Determination of vulval differentiation by means of intercellular signaling
24 Development of Drosophila Development in Drosophila illustrates progressive regionalization and specification of cell fateEarly development in Drosophila takes place within the egg caseThe first nine mitotic divisions occur rapidly without division of the cytoplasm and produce a cluster of nuclei within the egg (syncytium)Some nuclei migrate to the periphery of the embryo
25 Development of Drosophila At the posterior end, the pole cells (which form the germ line) become cellularizedAdditional mitotic divisions occur within the syncytial blastodermMembranes are formed around the nuclei, giving rise to the cellular blastodermFigure 11.13: Early development in Drosophila
26 Genes in Pattern Formation Cells in the blastoderm have predetermined developmental fates, with little ability to substitute for other, sometimes even adjacent, cellsThe earliest stages of Drosophila development are programmed in the oocyteMutations that affect oocyte composition or structure can upset development of the embryo
27 Genes in Pattern Formation Genes that function in the mother that are needed for development of the embryo are called maternal-effect genesDevelopmental genes that function in the embryo are called zygotic genesThe zygotic genes interpret and respond to the positional information laid out in the egg by the maternal-effect genes.
28 Genes in Pattern Formation Drosophila embryo and larva have segmental organizationThe segments are defined by successive indentations formed by the sites of muscle attachment in the larval cuticleThe parasegments are not apparent morphologically but include the anterior and posterior regions of adjacent segments
29 Genes in Pattern Formation The early stages of pattern formation are determined by segmentation genesThere are four classes of segmentation genes that differ in their times and patterns of expression in the embryo:1. coordinate2. gap3. pair-rule4. segment-polarityThe coordinate genes determine the anterior–posterior and dorsal–ventral axis of the embryo
30 Genes in Pattern Formation The gap genes are expressed in contiguous groups of segments along the embryo and establish the next level of spatial organization. Mutations in gap genes result in the gaps in the normal pattern of structures in the embryoThe pair-rule genes determine the separation of the embryo into discrete segments. Mutations in pair-rule genes result in missing pattern elements in alternate segments
31 Genes in Pattern Formation The segment-polarity genes determine the pattern of anterior–posterior development within each segment of the embryo. Mutations in segment-polarity genes affect all segments or parasegments in which the normal gene is activeInteractions among genes in the regulatory hierarchy ensure an orderly progression of developmental events
32 Figure 11.15: Segmental organization of the Drosophila embryo and larva
33 Homeotic GenesAs with many other insects, the larvae and adults of Drosophila have a segmented body planThe metamorphosis of the adult makes use of about 20 structures called imaginal disks present inside the larvaeFormed early in development, the imaginal disks give rise to the principal structures and tissues in the adult organismAmong the genes that transform the periodicity of the Drosophila embryo into adult body plan are two small sets of homeotic, or HOX, genes.
34 Homeotic GenesMutations in homeotic genes result in the transformation of one body segment into anotherMost HOX genes contain one or more copies of a characteristic sequence of about 180 nucleotides called a homeoboxHomeobox is highly conserved in evolutionHomeotic genes are transcriptional regulatorsHOX genes function at many levels in the regulatory hierarchy
35 Figure 11.21: Adult Drosophila with the imaginal disks from which they arise
36 Plant DevelopmentFloral development in Arabidopsis illustrates combinatorial control of gene expressionIn higher plants, differentiation takes place almost continuously throughout life in regions of actively dividing cells called meristems in both the vegetative organs and the floral organsAs groups of cells leave the proliferating region of the meristem and undergo further differentiation, their developmental fate is determined almost entirely by their position relative to neighboring cells.
37 Figure 11.27: Origin of distinct floral structures Plant DevelopmentThe flowers of Arabidopsis are composed of four types of organs arranged in concentric rings, or whorls. Each whorl gives rise to a different floral organ:whorl 1 yields the sepals,whorl 2 the petals,whorl 3 the stamens,whorl 4 the carpelsFigure 11.27: Origin of distinct floral structures
38 Plant DevelopmentMutations that affect floral development fall into three major classes, each with a characteristic phenotype:The phenotype lacking sepals and petals is caused by mutations in the gene ap1 (apetala-1)The phenotype lacking stamens and petals is caused by a mutation in either of two genes, ap3 (apetala-3) or pi (pistillata)The phenotype lacking stamens and carpels is caused by mutations in the gene ag (agamous)
39 Table 11.1: Floral Development in Mutants of Arabidopsis
40 Table 11.2: Domains of Expression of Gene Determining Floral Development
41 Plant Developmentap1, ap3, pi, and ag encode transcription factors that are members of the MADS box family of transcription factorsMADS box transcription factors include a common sequence motif consisting of 58 amino acids, and they are involved frequently in transcriptional regulation in plants and to a lesser extent in animals
42 Plant DevelopmentFlower development in Arabidopsis is controlled by the combination of genes expressed in each concentric whorlThe developmental identity of each concentric ring is determined by ap1, ap3, pi, and ag, each of which is expressed in two adjacent ringsTherefore, each whorl has a unique combination of active genesFigure 11.29: Flower
43 Programmed Cell DeathProgrammed cell death (PCD) occurs in developmental pathwaysPCD, or apoptosis, is a form of cell suicide that removes specific cells as part of pattern formationMutations in cell death genes may cause tissue malformations or abnormal cell growth patterns