Chapter 21 The Genetic Basis of Development

1. Chapter 21 The Genetic Basis of Development

2. Key Concepts • 21.1   Embryonic development involves cell division, cell differentiation, and morphogenesis • 21.2   Different cell types result from differential gene expression in cells with the same DNA • 21.3   Pattern formation in animals and plants results from similar genetic and cellular mechanisms • 21.4   Comparative studies help explain how the evolution of development leads to morphological diversity

3. How a complex multicellular organism develops from a single cell?

4. Use of model organisms • 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 lend themselves to the study of a particular question, are representative of a larger group, and are easy to grow in the lab.

5. For research aimed at uncovering the connections between genes and development, biologists have turned to organisms which have relatively short generation times and small genomes and about which much is already known. • Among the favorite model organisms in developmental genetics are the fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans, the mouse Mus musculus, the zebrafish Danio rerio, and the plant Arabidopsis thaliana. • Figure 21.2

6. Embryonic development involves cell division, cell differentiation, and morphogenesis • In the embryonic development of most organisms, a single–celled zygote (fertilized egg) gives rise to cells of many different types, each type with a different structure and corresponding function. • For example, an animal will have muscle cells that enable it to move and nerve cells that transmit signals to the muscle cells; a plant will have mesophyll cells that carry out photosynthesis and guard cells around stomata (pores) that regulate the passage of gases into and out of leaves.

7. Embryonic development must give rise not only to cells of different types but to higher–level structures arranged in a particular way in three dimensions • Within a multicellular organism, cells of different types are organized into tissues, tissuesinto organs, organsinto organ systems, and organ systems into the whole organism. • Thus, the process of embryonic development must give rise not only to cells of different types but to higher–level structures arranged in a particular way in three dimensions

8. Transformation of a zygote into an organism • Figure 21.3. • This transformation results from three interrelated processes: cell division, cell differentiation, and morphogenesis. • Through a succession of __________ cell divisions, the zygote gives rise to a large number of cells. • Cell division alone, however, would produce only a great ball of identical cells, nothing like an animal or plant.

9. During embryonic development, cells not only increase in number, but also undergo cell differentiation, the process by which cells become specialized in structure and function. • Moreover, the different kinds of cells are not randomly distributed but are organized into tissues and organs. The physical processes that give an organism its shape constitute morphogenesis, meaning “creation of form.”

10. The processes of cell division, differentiation, and morphogenesis overlap in time (Figure 21.4 ). • Morphogenetic events lay out the basic body plan very early in embryonic development, establishing, for example, which end of an animal embryo will be the head or which end of a plant embryo will become the roots. • These early events determine the body axes of the organism, such as the anterior–posterior (head–to–tail) axis and the dorsal–ventral (back–to–belly) axis.

11. Later morphogenetic events establish relative locations of structures within smaller regions of the embryo, such as the appendages on a fly′s body, the fins on a fish, or the digits on a vertebrate limb—and then within regions still smaller.

13. Morphogenesis in animals and plants • In addition to many shared developmental mechanisms, the development of animals and plants differs in two major ways: • In animals, but not in plants, movements of cells and tissues are necessary to transform the early embryo into the characteristic three–dimensional form of the organism. • In plants, but not in animals, morphogenesis and growth in overall size are not limited to embryonic and juvenile periods but occur throughout the life of the plant.

14. The structures responsible for a plant′s continual growth and formation of new organs are apical meristems, perpetually embryonic regions in the tips of shoots and roots. • In animals, ongoing development in adults is normally restricted to the generation of cells that must be continually replenished throughout the animal′s lifetime. Examples are blood cells, skin cells, and the cells lining the intestines.

15. During differentiation and morphogenesis, embryonic cells behave and function in different ways from each other, even though all of them have arisen from the same cell—the zygote.

16. Different cell types result from differential gene expression in cells with the same DNA • In earlier chapters, we have stated that differences between cells in a multicellular organism come almost entirely from differences in gene expression, not from differences in the cells′ genomes. (There are a few exceptions, such as antibody–producing cells; see Figure 43.11.) • Furthermore, these differences arise during development as regulatory mechanisms turn specific genes on and off. • Let′s now look at some of the evidence for this assertion

17. Evidence for Genomic Equivalence • The results of many experiments support the conclusion that nearly all the cells of an organism have genomic equivalence—that is, they all have the same genes. • What happens to these genes as a cell begins to differentiate? • Are these genes irreversibly inactivated during differentiation. For example, does an epidermal cell in your finger contain a functional gene specifying eye color, or has the eye–color gene been destroyed or permanently inactivated there?

18. How can we test for genomic equivalence? • One experimental approach for testing genomic equivalenceis to see whether a differentiated cell can generate a whole organism. • Such experiments were performed during the 1950s by F. C. Steward and his students at Cornell University, working with carrot plants (Figure 21.5 ).

19. Totipotency in Plants • They found that differentiated cells taken from the root (the carrot) and placed in culture medium could grow into normal adult plants, each genetically identical to the “parent” plant. • These results show that differentiation does not necessarily involve irreversible changes in the DNA. • In plants, at least, mature cells can dedifferentiate and then give rise to all the specialized cell types of the mature organism. • Any cell with this potential is said to be totipotent

21. Cloning • Using one or more somatic cells from a multicellular organism to make another genetically identical individual is called cloning, and each new individual made in this way can be called a clone (from the Greek klon, twig). • Plant cloning is now used extensively in agriculture. Indeed, if you have ever grown a new plant from a cutting, you have practiced cloning

22. Nuclear Transplantation in Animals • Differentiated cells from animals generally do not divide in culture, much less develop into the multiple cell types of a new organism. • Therefore, animal researchers had to use a different approach to the question of whether differentiated animal cells can be totipotent. • Their approach was to remove the nucleus of an unfertilized egg cell or zygote and replace it with the nucleus of a differentiated cell, a method called nuclear transplantation.

23. If the nucleus from the differentiated donor cell retains its full genetic capability, then it should be able to direct development of the recipient egg into all the proper tissues and organs of an organism.

24. Such experiments were conducted on frogs by Robert Briggs and Thomas King in the 1950s and extended by John Gurdon in the 1980s. • These researchers transplanted a nucleus from an embryonic or tadpole cell into an enucleated egg of the same species. The transplanted nucleus was often able to support normal development of the egg into a tadpole (Figure 21.6 ). • However, the “potency” of transplanted nuclei in directing normal development was inversely related to the age of the donor:the older the donor nucleus, the lower the percentage of normally developing tadpoles

26. From these results, we can conclude that something in the nucleus does change as animal cells differentiate. • In frogs and most other animals, nuclear potency tends to be restricted more and more as embryonic development and cell differentiation progress. • Research has shown that although the base sequence of the DNA usually does not change, the chromatin structure is altered in specific ways, usually involving chemical modifications of histones or DNA methylation (see Chapter 19).

27. However, these chromatin changes are sometimes reversible, and biologists agree that the nuclei of most differentiated animal cells have all the genes required for making the entire organism. • In other words, the various cell types in the body of an animal differ in structure and function not because they contain different genes, but because they express different sets of genes from a common genome

28. Reproductive Cloning of Mammals • Evidence that all cells in an organism have the same DNA also comes from experiments with mammals. • . Researchers have long been able to clone mammals using nuclei or cells from a variety of early embryos • But it was not known whether a nucleus from a fully differentiated cell could be “reprogrammed” to be _____________.

29. However, in 1997, Scottish researchers captured newspaper headlines when they announced the birth of Dolly, a lamb cloned from an adult sheep by nuclear transplantation from a differentiated cell (Figure 21.7 ). • These researchers achieved the necessary dedifferentiation of donor nuclei by culturing mammary cells in nutrient–poor medium. The researchers then fused these cells with sheep egg cells whose nuclei had been removed. The resulting diploid cells divided to form early embryos, which were implanted into surrogate mothers. One of several hundred implanted embryos successfully completed normal development, and Dolly was born

31. Later analyses showed that Dolly′s chromosomal DNA was indeed identical to that of the nucleus donor. • (Her mitochondrial DNA came from the _____ cell donor, as expected.) • In 2003, at age 6, Dolly suffered complications from a lung disease usually seen in much older sheep and was euthanized. Dolly′s premature death, as well as her arthritic condition, led to speculation that her cells were “older” than those of a normal sheep, possibly reflecting incomplete reprogramming of the original transplanted nucleus.

32. Since 1997, cloning has also been demonstrated in numerous other mammals, including mice, cats, cows, horses, and pigs. In most cases, the goal has been to produce new individuals; this is known as reproductive cloning.

33. Cloned animals of the same species do not always look or behave identically. In a herd of cows cloned from the same cell line, certain cows are dominant and others are more submissive. Another example is the first cloned cat, named Copy Cat (Figure 21.8 ). She has a calico coat, like her single female parent, but the color and pattern are different due to random ___ chromosome inactivation, which is a normal occurrence during embryonic development (see Figure 15.10). Clearly, environmental influences and random phenomena can play a significant role during development

35. Cloning of humans • The successful cloning of various mammals has heightened speculation about the cloning of humans. In early 2004, South Korean researchers reported success in the first step of reproductive cloning of humans. • In this work, nuclei from differentiated human cells were transplanted into unfertilized eggs from which the nuclei had been removed. • These eggs were stimulated to divide, and some reached the blastocyst stage, an early embryonic stage similar to the blastula stage in Figure 21.4.

36. Although the embryos were not allowed to develop beyond the blastocyst stage, the work of these researchers brings us one step closer to the possibility of human reproductive cloning, which raises unprecedented ethical issues. • However, problems associated with the cloning process have bought us a little more time for thought

37. Problems Associated with Animal Cloning • In most nuclear transplantation studies thus far, • only a small percentage of cloned embryos develop normally to birth. • And like Dolly, many cloned animals exhibit various defects. Cloned mice, for instance, are prone to obesity, pneumonia, liver failure, and premature death. • Scientists believe that even cloned animals that appear normal are likely to have subtle defects.

38. Reasons underlying the low efficiency of cloning and the high incidence of abnormalities • In the nuclei of fully differentiated cells, a small subset of genes is turned on and expression of the rest is repressed. • This regulation often is the result of epigenetic changes in chromatin, such as acetylation of histones or methylation of DNA (see Figure 19.4). • Many of these changes must be ___________ in the nucleus from a donor animal in order for genes to be expressed or repressed appropriately for early stages of development.

39. Researchers have found that the DNA in embryonic cells from cloned embryos, like that of differentiated cells, often has more methyl groups than does the DNA in equivalent cells from uncloned embryos of the same species. This finding suggests that the reprogramming of donor nuclei is not always complete. • Because DNA methylation helps regulate gene expression, misplaced methyl groups in the DNA of donor nuclei may interfere with the pattern of gene expression necessary for normal embryonic development

40. The Stem Cells of A nimals • Further support for the idea that cells become different by expressing different sets of genes from the same genome comes from the study of a group of cells called stem cells. • A stem cell is a relatively unspecialized cell that can both reproduce itself indefinitely and, under appropriate conditions, differentiate into specialized cells of one or more types. • Thus, stem cells are able both to replenish their own population and to generate cells that travel down various differentiation pathways.

41. Many early animal embryos contain totipotent stem cells, which can give rise to differentiated cells of any type. • Stem cells can be isolated from early embryos at the blastula stage or its human equivalent, the blastocyst stage (Figure 21.9 ). In culture, these embryonic stem cells reproduce indefinitely; and depending on culture conditions, they can differentiate into various specialized cells, including even eggs and sperm

43. The adult body also has a variety of stem cells, which serve to replace nonreproducing specialized cells as needed. • In contrast to totipotent embryonic stem cells, adult stem cells are said to be pluripotent, able to give rise to multiple but not all cell types. • For example, stem cells in the bone marrow give rise to all the different kinds of blood cells (see Figure 21.9), and those in the intestinal wall regenerate the various cells forming the lining of the intestine.

44. To the surprise of many, we have recently discovered that the adult brain contains stem cells that continue to produce certain kinds of nerve cells there. • Although adult animals have only tiny numbers of stem cells, scientists are learning to identify and isolate these cells from various tissues and, in some cases, to grow them in culture. • Taking this research further, scientists have found that with the right culture conditions (for instance, the addition of specific growth factors), cultured stem cells from adult animalscan differentiate into multiple types of specialized cells.

45. Research with embryonic or adult stem cells is providingvaluable information about differentiation and has enormous potential for medical applications. • The ultimate aim is to supply cells for the repair of damaged or diseased organs: for example, insulin–producing pancreatic cells for people with diabetes or certain kinds of brain cells for people with Parkinson′s disease or Huntington′s disease. • Currently, embryonic stem cells are more promising than adult stem cells for such applications, but because the cells are derived from human embryos, their use raises ethical and political issues

46. Therapeutic cloning • When the major aim of cloning is to produce embryonic stem cells to treat disease, the process is called therapeutic cloning. • Although most people believe that reproductive cloning of humans is unethical, opinions vary about the morality of therapeutic cloning

47. 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

48. Problems Associated with Animal Cloning • In most nuclear transplantation studies, only a small percentage of cloned embryos have developed normally to birth • Many epigenetic changes, such as acetylation of histones or methylation of DNA, must be reversed in the nucleus from a donor animal in order for genes to be expressed or repressed appropriately for early stages of development

50. Transcriptional Regulation of Gene Expression During Development • As the tissues and organs of an embryo take shape, the cells become visibly different in structure and function. • These observable changes are actually the outcome of a cell′s developmental history extending back to the first mitotic divisions of the zygote. • However, the earliest changes that set a cell on a path to specialization are subtle ones, showing up only at the molecular level.