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Introduction
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All types of somatic cells (all cells except gametes) retain all the genes that were present in the fertilized egg.
Cellular changes during development and cell differentiation result from differential gene expression.
The Processes of Development
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Development is a series of progressive changes in shape, form, and function that occur during an organism’s
life cycle. (See Figure 19.1.)
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The earliest stage is called the embryonic stage.
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In some species, embryos are contained in the starchy matrix of a seed.
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In other species, embryos are contained in egg shells or the uterus.
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Embryos typically acquire food directly or indirectly from a parent.
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Embryonic stages precede birth; development continues until death.
Development consists of growth, differentiation, and morphogenesis
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Growth occurs by cell division and/or expansion.
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Repeated mitotic cell divisions increase cell number.
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Plants use cell elongation to increase size early in development.
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Animal embryos use cell division to increase cell number, but the size of the organism often changes only
slightly during the early embryonic period.
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Differentiation is the process that distinguishes cells from one another structurally and functionally.
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Cells of an embryo have fewer functional types, but each cell has the potential to develop in many different
ways.
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As development proceeds, the possibilities available to individual cells narrow, until each cell’s fate is
determined and the cell has differentiated.
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Morphogenesis is the shaping of the multicellular body and its organs. (See Figure 19.1.)
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Morphogenesis is the organization of differentiated tissues into specific structures.
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In plants, movement of cells is limited, because cell walls adhere to each other and restrict movement.
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Animal cells can move, and this movement is of great importance during morphogenesis.
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Programmed cell death is important in the orderly development of both plant and animals.
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(See Videos 19.1–19.4.)
As development proceeds, cells become more and more specialized
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Staining early embryo cells can produce fate maps revealing which adult structures derive from which part of
an embryo.
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Moving a section of cells from a region of an early frog embryo to another region causes the cells to
differentiate appropriately for the new—not the old—location. (See Figure 19.2.)
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Cells do not generally maintain this developmental plasticity, however.
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Later in development, transplanted tissue from an embryo develops into the original type of tissue, regardless
of its new location. At this point the tissue is said to be determined.
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Cell determination is influenced by the extracellular environment and the contents of the cell acting on the
cell’s genome.
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Determination precedes differentiation—the actual changes in biochemistry, structure, and function of cells.
The Role of Differential Gene Expression in Cell Differentiation
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Differentiation results from differential gene expression.
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This means that it results from the differential regulation of transcription, posttranscriptional events, and
translation.
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The fertilized egg is a totipotent cell. That is, it can give rise to all other cell types of an organism.
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As the cells divide, become determined, and then differentiate, they lose totipotency.
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When a cell becomes specialized (as a nerve cell, for example), it is said to have differentiated.
With differentiation, there is generally no irreversible change in the genome
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Generally, mature cells contain all the genetic information found in the zygote.
There are a few exceptions:
Red blood cells lose their nuclei as they mature.
Tracheid cells of plants die before they can become functional water-transporting structures.
In both of these cases, the absence of a functional nucleus explains their irreversibility.
Many differentiated cells can retain totipotency.
Totipotency in plants:
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In general, differentiation in plant cells can be reversed more easily than differentiation in animal cells.
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A carrot root cell can be tricked into forming a whole new plant. (See Figure 19.3.)
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Since the new plant is genetically identical to the original plant, it is called a clone.
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The ability to generate an entire plant from a single cell is invaluable to biotechnology.
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Totipotency in early embryonic animal cells:
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Robert Briggs and Thomas King replaced the nucleus of an unfertilized frog egg with the nucleus of a
somatic cell from an early frog zygote.
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Many of these nuclear transplant operations resulted in the formation of normal early embryos.
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These experiments led to two important conclusions.
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No information is lost from the nuclei of cells as they pass through the early stages of embryonic
development (a principle known as genomic equivalence).
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The cytoplasmic environment around a nucleus can modify its fate.
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Rhesus monkeys have also been successfully produced using nuclear transplantation from an 8-cell embryo.
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This same method permits genetic screening of very early embryos in humans:
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A single cell is removed from an 8-cell human embryo.
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The cell is tested for harmful genetic conditions.
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Each remaining cell, being totipotent, can be stimulated to divide and form a normal embryo.
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Totipotency in adult somatic cells:
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Until recently (late 1990s), successful cloning of animals from fully differentiated cells was difficult.
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Cells from an adult ewe (a female sheep) have served as a source of donor nuclei for cloning.
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In 1996, Ian Wilmut and colleagues used the nucleus of an udder cell starved of nutrients, which arrested the
cell cycle in G1 phase. (See Figure 19.4.)
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This cell was fused with an enucleated egg from a different ewe and stimulated to enter the S phase.
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After several cell divisions, the early embryo was transplanted to the womb of a surrogate mother ewe.
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Out of 227 successful fusions, one lamb, named Dolly, survived to birth.
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The ultimate goal of sheep cloning is to develop transgenic (genetically modified) ewes that can produce
drugs in their milk.
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1-antitrypsin, for example, is used to treat people with cystic fibrosis.
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Other mammals that have been cloned using this method include mice, cows, and goats. (See Figure 19.5.)
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A human tumor called a teratocarcinoma is an example of nuclear totipotency gone awry.
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In this type of tumor, a differentiated cell reverts to an undifferentiated stage and starts dividing, forming a
tumor.
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Some cells in the tumor differentiate, forming kidney tubes, hair, or even teeth.
Stem cells can be induced to differentiate by environmental signals
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Stem cells are undifferentiated dividing cells that are found even in adults.
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A few examples are those found in bone marrow, skin, and intestine, tissues which need frequent cell
replacement.
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An interesting example of a stem cell’s becoming a different type of stem cell in response to altered
environmental signals has recently been discovered in mice.
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Brain stem cells were transplanted to bone marrow, where they became bone marrow stem cells and produced
blood cells.
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The brain stem cells normally differentiate into nerve cells.
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The reverse experiment resulted in bone marrow cells that differentiated into brain cells.
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These experiments indicate that the cell’s environment determines what a stem cell will do.
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Stem cells with the greatest totipotency are the cells of early embryos.
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If these cells are removed and then later injected into a blastocyst, they mix with resident cells, and the
individual develops to form all cell types.
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Embryonic stem cells can be induced to differentiate using certain signal molecules.
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Treatment of mouse embryonic stem cells with a derivative of vitamin A causes them to form nerve cells.
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Other growth factors induce them to form blood cells.
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Possibly, in the future, manipulation and customizing of embryonic cells in culture will make new disease
treatments possible. (See Figure 19.6.)
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Human embryos made for in vitro fertilization are a potential source of embryonic stem cells.
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A problem can arise if embryonic stem cells are used to form tissues for a transplantation.
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Genetic differences between the donor and recipient may result in rejection of the transplant by the
recipient’s immune system.
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A procedure called therapeutic cloning has been proposed to address this problem.
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This process involves fusing a cell nucleus from the recipient with an enucleated egg cell from a female
donor.
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When this fused cell is stimulated to divide, embryonic stem cells form that are genetically identical to the
recipient’s.
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These cells can be induced to differentiate into the desired tissue for transplantation without the risk of
immune system rejection.
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Progress in this approach has been slow but steady.
Genes are differentially expressed in cell differentiation
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There appears to be genome constancy or equivalence in all somatic cells.
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-globin is synthesized in blood cells, but the DNA coding for it can be found in other cells, such as brain
cells.
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To understand what determines such differential gene expression, myoblasts, precursors to muscle cells, have
been studied for expression of muscle-specific genes.
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MyoD1 is the first gene switched on.
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It codes for a helix-loop-helix type transcription factor (MyoD1), a DNA-binding protein.
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MyoD1 protein binds to the promoters of muscle-specific genes, switching them on.
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It also binds to its own promoter, keeping itself in the myoblasts and their descendants.
The Roles of Cytoplasmic Segregation and Induction in Cell
Determination
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Two general mechanisms for producing signals used for cellular programming of differential gene expression
are cytoplasmic segregation and induction.
Polarity results from cytoplasmic segregation
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Polarity is an early and obvious event in development.
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Polarity includes the establishment of the most obvious differentiation, such as anterior–posterior ends and
dorsal–ventral surfaces.
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When an egg divides, the resulting cells receive unequal amounts of materials that were distributed unevenly
in the cytoplasm of the zygote.
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These differences in cytoplasmic makeup account for some of the earliest differentiation in embryos.
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Sea urchin eggs have polarity at the 8-cell stage.
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If an embryo is divided into two parts, left and right halves, normal-shaped development of dwarfed larvae
occurs.
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If the sea urchin embryo is cut into upper and lower halves, the upper half cannot form a larva and the lower
half is misshapen. (See Figure 19.7 and Animated Tutorial 19.1.)
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Clearly, at least one factor essential for development is in the bottom half of the egg only.
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Experiments have established the existence of such cytoplasmic determinants in the eggs of many organisms.
(See Figure 19.8.)
Tissues direct the development of their neighbors by secreting inducers
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An early discovery in development was the induction of cells to form lens cells in frogs.
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The forebrain bulges out at both sides of the future head region, forming optic vesicles.
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These cells expand until they reach the cells at the surface of the head.
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The surface tissue thickens, forming the placodes of the two lenses.
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The placodes bend inward at their margins and constrict and pinch to form a structure that then differentiates
into lenses.
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If the growing optic vesicles are cut away before reaching the surface, no lenses form.
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If an impermeable barrier is placed between the optic vesicle and the surface tissue, lenses still do not form.
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The induction of lenses appears to be a two-way street between the optic vesicle and the surface tissue. (See
Figure 19.9.)
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The optic vesicle induces lens development by sending a signal—an embryonic inducer—to surface tissue.
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The developing lenses influence the size of the optical cups.
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The developing lens also induces the surface tissue to develop into a cornea to permit light entry.
Single cells can induce changes in their neighbors
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The development of the roundworm Caenorhabditis elegans (also called a nematode) has been studied
extensively.
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Development from egg to larva takes just 8 hours at 25ºC.
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Development can be observed easily under low magnification because of the transparency of the embryo.
(See Figure 19.10.)
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Scientists have determined the source of each of the 959 somatic cells of the adult form.
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One cell, called an anchor cell, induces the vulva to form.
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If the anchor cell is destroyed, no vulva forms.
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This prevents eggs from being laid.
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The parent bearing this “bag of worms” is consumed by its own progeny.
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The anchor cell controls the fates of six cells on the ventral surface through two molecular switches.
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Each of the six cells has three possible fates:
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It might become a primary vulval precursor.
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It might become a secondary vulval precursor.
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It might simply become part of the worm’s surface.
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The anchor cell produces an inducer, which controls the activation or inactivation of specific genes in
responding cells. The inducer diffuses out of the cell and interacts with adjacent cells, setting the “track” for these cells.
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Cells that get enough inducer become vulval precursors.
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Those farther away from the anchor get less inducer and become epidermis.
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The primary vulval precursor cell produces its own inducer, influencing the two neighboring cells to become
secondary vulval precursors.
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The primary inducer in nematode vulval differentiation is homologous to the mammalian growth factor called
epidermal growth factor (EGF).
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This nematode factor, called LIN-3, binds a receptor on the surface of a vulval precursor cell.
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This activates a protein kinase cascade that includes the Ras protein and MAP kinases. (See Figure 15.9.)
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The end result is increased transcription of genes involved in vulval cell differentiation.
The Role of Pattern Formation in Organ Development
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Pattern formation, the spatial organization of a tissue or organism, is inextricably linked to morphogenesis,
the appearance of body form.
Some cells are programmed to die
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Apoptosis is programmed cell death. (See Figure 9.19.)
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It is caused by the activation of “death” genes.
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Of the 1,090 somatic cells produced by C. elegans, 131 cells are programmed to die.
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The genes ced-4 and ced-3 appear to control this process.
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A third gene, ced-9, codes for an inhibitor of ced-4. Therefore, when cell death is required, ced-3 and ced-4
are active and ced-9 is inactive.
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A similar system of cell death genes exists in humans.
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Early human embryos have webs between fingers and toes. (See Figure 19.11.)
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Between day 41 and day 56, the cells of the webbing die, freeing individual fingers and toes.
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The enzyme caspase stimulates apoptosis and is homologous to ced-3.
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The protein in humans that inhibits apoptosis is bcl-2, which is similar to the protein encoded by the C.
elegans gene ced-9.
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So, despite some 600 million years of evolutionary separation, nematodes and humans have similar genes
controlling programmed cell death.
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One form of cancer, follicular large-cell lymphoma, is caused by overexpression of bcl-2 in some white blood
cells. Since bcl-2 inhibits apoptosis, these cells continue to divide instead of dying.
Plants have organ identity genes
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The identity of the whorls from which floral organs develop (i.e., sepals, petals, stamens, and carpels) is
determined by a group of genes.
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These genes have been best described in Arabidopsis thaliana, also called the mouse-ear cress.
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This plant is small, has a relatively small genome (10 chromosomes with 80 million base pairs), produces
many seeds (about 1,000), and develops rapidly (6 weeks from seed to plant).
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It also is easy to produce mutations in Arabidopsis.
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Normal Arabidopsis flowers have four whorls of organs. Homeotic mutants have the wrong organs in
particular whorls (See Figure 19.12.)
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Flower development involves three different organ identity genes, which act as molecular switches and code
for proteins that act in combination with one another.
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Whorl 1 expresses gene A; whorl 2 expresses genes A and B; whorl 3 expresses genes B and C; and whorl 4
expresses gene C.
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The products of these genes are transcription factors that form dimers (two subunits).
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The composition of the dimer determines which other genes will be activated by the transcription factor.
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This is referred to as combinatorial gene regulation.
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Many transcription factors, including the A, B, and C proteins, have a DNA-binding domain called the
MADS box.
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A gene called leafy controls the transcription of the ABC genes.
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Plants with a mutation that causes the underexpression of this gene produce leaves but no flowers. (See
Figure 19.13.)
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Research that increases the understanding of flowering could be used to increase food production.
Morphogen gradients provide positional information
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Certain cells in both plants and animals seem to “know” where they are within the organism. This is called
positional information.
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Positional information usually comes in the form of a signal created by a concentration gradient of a
morphogen.
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There are two requirements for a signal to be considered a morphogen.
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It must directly affect target cells.
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Different concentrations of the signal must cause different effects.
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A vertebrate limb develops from a round bud.
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The cells that become the bones and muscles of the limb must receive positional information, then organize
to shape properly.
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A group of cells at the posterior base of the bud makes a morphogen called BMP2, whose gradient
determines the anterior–posterior axis of the limb.
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Cells that get the highest dose of BMP2 make the thumb, and the smallest dose results in the little finger.
The Role of Differential Gene Expression in Establishing Body
Segmentation
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worms.
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Drosophila body segments are clearly different from one another, unlike the body segments of segmented
The head is composed of several fused segments.
There are three different thoracic segments.
There are eight abdominal segments.
The 13 seemingly identical segments of the Drosophila larva correspond to the specialized adult segments.
The process of differentiating these segments begins with establishing the polarity of the embryo.
Maternal effect genes encode morphogens that determine polarity
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In Drosophila, unequal distribution of morphogens helps establish the basic coordinates.
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Morphogens are mRNAs and proteins.
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The morphogen molecules are products of specific maternal effect genes distributed by the mother to the
eggs.
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The maternal effect genes are transcribed in the mother’s ovarian cells, which support the developing egg.
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It is their influence that determines the dorsal–ventral and anterior–posterior axes of the embryo.
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Two maternal effect genes are bicoid and nanos. (See Figure 19.14.)
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The bicoid gene controls anterior larval development, while the nanos gene controls posterior larval
development. Therefore, these morphogens gradate through the length of the larva, with high levels of Bicoid protein
and low levels of Nanos protein in the anterior regions, and the reverse condition in the posterior region.
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A mutation in one of these genes can affect the anterior– posterior development of the larva.
Segmentation and homeotic genes act after the maternal effect genes
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Segmentation genes influence the number, boundaries, and polarity of the body segments.
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The maternal effect gene products influence the axes of the embryo when there are 6,000 nuclei existing in a
common cytoplasm. (See Figure 19.15 and Animated Tutorial 19.2.)
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After the nuclei are isolated into different cells, three classes of segmentation genes act one after another.
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Gap genes organize large areas along the anterior–posterior axis.
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Pair rule genes divide the embryo into units of two segments each.
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Segment polarity genes determine the boundaries of anterior–posterior segments.
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Finally, homeotic genes are expressed along the length of the body and tell the segments what to become.
Drosophila development results from a transcriptionally controlled gene
cascade
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Development is the result of a sequence of changes, each triggering the next.
The unfertilized egg begins with stored mRNA.
Early embryos do not carry out transcription.
The stored mRNA is made prior to fertilization and supports protein synthesis during early development.
The mRNA for Bicoid protein is located at the future anterior end of the Drosophila egg.
After fertilization, the egg is laid and nuclear division occurs.
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The embryo consists of a multinucleated cell called a syncytium.
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Then, Bicoid mRNA is translated and Bicoid protein is synthesized.
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The Bicoid protein diffuses away toward the posterior end.
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At the posterior, Nanos protein forms a gradient in the other direction. (See Figure 19.14.)
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Each nucleus in the developing embryo is exposed to a different concentration ratio of Bicoid and Nanos
proteins.
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These morphogens regulate the expression of the gap genes.
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Bicoid protein affects specific transcription.
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Nanos affects specific translation.
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High Bicoid at the anterior turns on a gap gene (hunchback), while simultaneously turning off another gap
gene (Krüppel).
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Nanos at the posterior reduces hunchback.
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The gap genes control the expression of pair rule genes.
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The pair rule gene products control the segmentation polarity genes.
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Each homeotic gene is expressed over a characteristic portion of the embryo. (See Figure 19.15.)
Homeotic mutations produce changes in segment identity
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One mutant of a homeotic gene (Antennapedia) causes legs to grow in the place of antennae.
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Another, bithorax, causes an extra pair of wings to grow in a thoracic segment.
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Bithorax is not a single gene but a gene cluster.
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Homeotic genes provide functional identity to each segment.
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Drosophila was found to have two clusters, one for segments at the front of the fly called the Antennapedia
cluster and another called the bithorax cluster.
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The genes within a cluster are arranged in an order on the chromosome that is collinear to their expression in
segments.
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There are DNA sequences in common within the homeotic genes of both clusters.
Homeobox-containing genes encode transcription factors
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A 180-base-pair DNA sequence that is common to the homeotic genes is called the homeobox.
It codes for a 60-amino-acid sequence called the homeodomain, which binds DNA.
The homeodomain has the helix-turn-helix motif.
Each homeodomain recognizes a specific DNA sequence.
Homeotic genes code for transcription factors.