Chapter 11 The Genetic Control of Development

1. Chapter 11 The Genetic Control of Development

2. Genes and Development • The genotype determines not only the events that take place in development but also the temporal order in which the events unfold • A 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 egg • Genetic 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 transcription • The alternative mating-type alleles MATa(mating type a) and MAT(mating type  ) both express a set of haploid-specific genes, including HO forthe 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 include • secretion of a mating peptide • production 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 fusion • In a cell of mating type a, the MATa region is transcribed and a polypeptide called a1 is produced • a1 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 genes • The 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 2 • The 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 asg • Because 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 complex • This 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 sexes • In C. elegans, the two sexes are the hermaphrodite and the male • The hermaphrodite contains two X chromosomes (XX), produces both functional eggs and functional sperm, and is capable of self-fertilization • The male produces only sperm and fertilizes the hermaphrodites • There 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 next • As a result each sex shows the same geometry in the number and arrangement of somatic cells • The hermaphrodite contains exactly 959 somatic cells, and the male contains exactly 1031 somatic cells • The 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 cells • Lineage diagram is a sort of cell pedigree that shows each cell division and indicates the terminal differentiated state of each cell • Cell 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 lineage • Cell 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 themselves • Cells 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 Development • Many 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 gene • Most genes that affect development are active in more than one type of cell

17. Genes and Development • Complex lineages often include simpler, genetically determined sublineages within them • The lineage of a cell may be triggered autonomously within the cell itself or by signaling interactions with other cells • Regulation 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 Fate • Genes that control cell fate can be identified by the unusual property: dominant and recessive mutations have opposite effects • If 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 Fate • Recessive mutations often result from loss of function—the mRNA is not produced or the protein is inactive • Dominant mutations often result from gain of function—the gene is overexpressed or is expressed at the wrong time

20. Lineage Mutations • In C. elegans, a relatively small number of genes have dominant and recessive alleles that affect the same cells in opposite ways • Among them is the lin-12 gene, which controls developmental decisions in a number of cells • The molecular structure of the lin-12 gene product is typical of a transmembrane receptor protein containing regions that span the cell membrane

21. Figure 11.5: Recessive loss-of-function mutants/ dominant gain-of-function mutants

22. Lineage Mutations • Cells can determine the fate of other cells through ligands that bind with their transmembrane receptors • lin-3 expressed in anchor cell controls the fate of other cells in the development of the vulva • Loss 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 fate • Early development in Drosophila takes place within the egg case • The 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 cellularized • Additional mitotic divisions occur within the syncytialblastoderm • Membranes are formed around the nuclei, giving rise to the cellular blastoderm Figure 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, cells • The earliest stages of Drosophila development are programmed in the oocyte • Mutations 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-effectgenes • Developmental genes that function in the embryo are called zygotic genes • The 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 organization • The segments are defined by successive indentations formed by the sites of muscle attachment in the larval cuticle • The 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 segmentationgenes • There are four classes of segmentation genes that differ in their times and patterns of expression in the embryo: 1. coordinate 2. gap 3. pair-rule 4. segment-polarity • The 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 embryo • The 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 active • Interactions 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 Genes • As with many other insects, the larvae and adults of Drosophila have a segmented body plan • The metamorphosis of the adult makes use of about 20 structures called imaginal disks present inside the larvae • Formed early in development, the imaginal disks give rise to the principal structures and tissues in the adult organism • Among the genes that transform the periodicity of the Drosophila embryo into adult body plan are two small sets of homeotic, orHOX, genes.

34. Homeotic Genes • Mutations in homeotic genes result in the transformation of one body segment into another • Most HOX genes contain one or more copies of a characteristic sequence of about 180 nucleotides called a homeobox • Homeobox is highly conserved in evolution • Homeotic genes are transcriptional regulators • HOX 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 Development • Floral development in Arabidopsis illustrates combinatorial control of gene expression • In 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 organs • As 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. Plant Development • The 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 carpels Figure 11.27: Origin of distinct floral structures

38. Plant Development • Mutations 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 Development • ap1, ap3, pi, and ag encode transcription factors that are members of the MADS box family of transcription factors • MADS 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 Development • Flower development in Arabidopsis is controlled by the combination of genes expressed in each concentric whorl • The developmental identity of each concentric ring is determined by ap1, ap3, pi, and ag, each of which is expressed in two adjacent rings • Therefore, each whorl has a unique combination of active genes Figure 11.29: Flower

43. Programmed Cell Death • Programmed cell death (PCD) occurs in developmental pathways • PCD, or apoptosis, is a form of cell suicide that removes specific cells as part of pattern formation • Mutations in cell death genes may cause tissue malformations or abnormal cell growth patterns