Cell Structure

Nancy J Lane, University of Cambridge, Cambridge, UK

Cells are living entities made up of a central nuclear region which contains the hereditary material, surrounded on all sides by cytoplasm, which, encompassed by a delimiting membrane, contains all the structures required for biological processes, such as making protein and extracting utilizable energy from food. These events may occur in separate compartments, the organelles, which include the endoplasmic reticulum, the Golgi apparatus, the mitochondria, the chloroplasts and the lysosomes; there is also an internal cytoskeleton.

Introductory article
Article Contents
. Prokaryotic and Eukaryotic Cells . The Nucleus and Genetic Information . Cell Division: Mitosis and Meiosis . Cell Cycles . The Cell Surface and Plasma Membrane . Internal Membranes and Subcellular Compartments: Organelles . Cytoskeleton . Multicellularity

Prokaryotic and Eukaryotic Cells

Cells are the subunits of all living systems, both plant and animal, and are of two major types: prokaryotic and eukaryotic. Prokaryotic cells are relatively small (15 mm in diameter) and simple, and are those that make up singlecelled microorganisms or bacteria. They are so-called because each of them lacks a denitive nucleus (or karyon), having only a central area in the cell cytosol where the genetic material, the deoxyribonucleic acid (DNA), is found. This lies naked, without associated protein, usually in a circular conguration. As these cells possess no distinct membrane-bound nucleus, they are prokaryotic. Eukaryotic (with a karyon) cells, in contrast, are the constituents of all multicellular organisms. They possess a distinct nucleus, bounded by a double nuclear envelope, wherein lies the genetic material in the form of the DNA-containing chromosomes. This DNA is in the form of linear strings of genes, and is combined with histone protein to make up chromatin. Such cells are much larger than prokaryotic cells, ranging in diameter from 10 mm up to many millimetres (of which egg cells are the largest), although averaging about 3060 mm in diameter. The reason for this disparity in size is in large part due to the fact that prokaryotic cells lack organelles, or internal compartmentalization. Eukaryotic cells, on the other hand, have extensive subcellular compartments in the form of dierent kinds of organelles (Figure 1). The prokaryotic cell type is suciently small for simple diusion alone to allow for the ecient transport and exchange of materials within its substance; no compartments are required. The cells contain a cytosol, or ground cytoplasm, which contains all the enzymes (catalysts) and building blocks (metabolites) to synthesize cell components; prokaryotic cells are bounded by a plasma (cell) membrane, and then sometimes also by a second, outer cell membrane. They also possess an outer cell wall, which provides support and strength to maintain the integrity of the cell during environmental stress.

. Intercellular Junctions: Communication and Adhesion . Differentiation . Communication

The Nucleus and Genetic Information

Eukaryotic nuclei contain the genetic material, DNA, in the form of discrete chromosomes; these are present in variable numbers, depending on the species. All cells in a given individual contain the same amount of DNA, save for the germline cells. The DNA is associated with histone protein in the form of nucleosomes, which look like beads on a string in the unfolded state between cell divisions.
Prokaryotic cell Recycling membrane

Mitochondrion Nucleus Lysosome Nucleolus Exocytosis

Ribosomes Secretory granule

Endoplasmic reticulum

Golgi

Figure 1 Cross-sectional diagram of a generalized eukaryotic cell, revealing the central DNA-containing nucleus with peripheral cytoplasm, in which can be found many organelles, such as mitochondria, lysosomes, cisternae of rough endoplasmic reticulum, saccules of the Golgi apparatus, secretory granules being released by exocytosis, and endosomes forming by endocytosis. The mitochondria are thought to have arisen by the endocytotic uptake of prokaryotic cells.

ENCYCLOPEDIA OF LIFE SCIENCES 2001, John Wiley & Sons, Ltd. www.els.net

Cell Structure

These coil and fold up, or are condensed, into sausageshaped structures in dividing eukaryotic cells that can be seen with the light microscope. This is not the case in prokaryotic cells where the DNA remains naked and does not condense into visible structures during cell division.

Cell Division: Mitosis and Meiosis

Mitosis
Cell turnover and programmed cell death (apoptosis) occur as normal events in biological systems. Cell replacement occurs by cell division. All living cells have the capacity to divide into two identical daughter cells, by a process called binary ssion (a mitotic-like process) (in prokaryotic cells) or mitosis (in eukaryotic cells). In mitosis, nuclear chromosomes replicate into two genetically identical sister chromatids which initially remain together. The act of replication occurs during S (synthesis) phase which punctuates interphase, the period between successive acts of mitosis. Replication of chromosomes is actually replication of the DNA double helix which occurs at a replication fork, involving a host of dierent enzymes. After replication in the S phase, there is a gap (G) phase before the cell enters prophase, the rst stage of mitosis. The sister chromatids then move on to the metaphase plate, of the so-called spindle of microtubules, fully divide and separate into two distinct chromosomes, which are moved in opposite directions to two poles during anaphase and telophase, the last stages of mitosis. In animal cells, after division of the cytoplasm into two, by pinching together (cytokinesis), two identical daughter cells result, and each reverts back into the interphase, or resting, state. In plant cells, a cell membrane is laid down by a phragmoplast, which gradually extends out to the cell edges, after which a cell wall of cellulose is formed.

chromosomes)) sperm cell fertilizes the haploid (x1n) egg, a new, diploid (x2n) individual again results. This enables parental germ cell fusion (haploid egg fertilized by a haploid sperm) to form a diploid zygote, which gives rise to a genetically unique diploid individual, dierent from both parents (but with a genetic contribution from each), which is the ospring, or lial (F1) generation. Genetic exchange also occurs in prokaryotic cells, but it is a horizontal, not vertical, recombination, and only parts of the genome (the total DNA of any organism) are exchanged. This exchange is triggered by a vector (carrier) which may be a plasmid, an extra bit of DNA in the form of an F1 factor, or even part of a virus which has infected the cell. Hence genetic engineering results from genes, attached to vectors, being integrated into a dierent, recipient cell, and subsequently expressing the proteins for which the integrated genes code, which would not normally be synthesized in the recipient cell.

Cell Cycles
The dierences in overall nuclear arrangements in prokaryotic and eukaryotic cells mean that there are signicant dierences in the cell cycle of the two kinds of cells that is, in the timing and the way in which their chromosomal DNA is replicated and two new cells form from the original. The cell cycle is much more protracted in eukaryotic than prokaryotic cells. The period between cell divisions is called interphase, and, far from being an actual resting stage, it is then that the synthetic activity of the cell occurs, i.e. the making of ribonucleic acid (RNA) and protein, as well as the replication of the DNA. In interphase the nuclear DNA makes messenger RNA (mRNA) molecules, which leave the nucleus and go to the cytoplasm, to tell the ribosomes which proteins to synthesize. These are, therefore, informational molecules and the particular mRNA made will depend on the cell type, which will in turn depend on the tissue in question. Not all genes (a gene 5 the DNA producing the message to make a particular protein) will be active at all times. Dierent genes are turned on at dierent stages in development. There are also distinctions in the modications of mRNA made in eukaryotic compared with prokaryotic cells. The way gene action or the expression of genes (the making of mRNA from DNA and then making protein from the mRNA) is controlled, and the recognition systems for targeting of molecules between and within cells to activate such expression, also dier in the two cell types. Dierent, too, is the structure of the cytoplasmic ribosomes, or the tiny RNP particles (RNP 5 RNA plus protein) in the two kinds of cell. Ribosomes are distinguishable by cell biologists by their sedimentation characteristics in sucrose density gradients. They are, as a result, called 70S (prokaryotic) or 80S

Meiosis
Eukaryotic germline cells, contained in the sexual organs of animals and plants, the testis (or anther) and ovary (or ovule), undergo reciprocal genetic exchange, or gene recombination, during a process called meiosis, in which chromosomal crossing-over occurs. This takes place when diploid germ cells (with two sets of chromosomes) are being transformed into haploid cells (with just one set of chromosomes), and is a way of ensuring genetic variability in the germ cells (and hence in the next generation). Most organisms, plant and animal, are diploid. Meiotic division takes place when the germ cells (eggs and sperm or ovary and pollen) are being produced. Every germ cell must become haploid by undergoing a reduction division, so that when the haploid (x1n (where n 5 number of sets of
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(eukaryotic) ribosomes, reecting the number of Svedberg (S) units they exhibit. These are the protein-making machinery of all cells and have roughly the same function in both cell types, in spite of their diering S values.

The Cell Surface and Plasma Membrane

The cell surface and the cell (plasma) membrane also dier between eukaryotic and prokaryotic cells. As mentioned earlier, the cell surface of some prokaryotic cells is covered with a double membrane, as well as an external cell wall of crosslinked polysaccharides. A mucous coat often also lies around this outer wall. Of eukaryotic cells, those of plants also have an external cell wall, which is primarily composed of cellulose brils to give strength and rigidity. Cells of animals lack a cell wall; instead, they possess a glycocalyx of carbohydrate-rich transmembrane molecules that straddle the outer plasma membrane and enable adjacent cells to stick to one another, albeit at a set distance, 1520 nm. This spacing permits the recognition, by circulating chemical signals, of membrane-associated cellular receptor or adhesion molecules. The plasma membrane is a lipid bilayer in which are inserted a number of proteins. These are arranged in a variety of patterns that are related to their function, and have the capacity to move translaterally like icebergs in the bilayer sea of lipid. The membrane is therefore said to have a uid character. It is not possible to resolve the details of the molecular structure of a membrane even with the high powered electron microscope, which can achieve a resolution of 12 nm. As molecular subunits are too small to be resolved as separate entities, models of the plasma membrane have been designed over the years to try to explain its molecular structure. The rst model was devised by Davson and Danielli in the early part of the twentieth century and was called the DavsonDanielli lipid bilayer model. With the advent of the electron microscope, J. David Robertson, around 1960, looked at the ultrastructure of membranes and proposed a new model which he called the unit membrane model; this suggested that all membranes shared a single, unifying structure. After the development of a technique called freeze-fracturing, it was possible to observe the three-dimensional arrangements of putative protein particles in the bilayer sea of lipid. These particles were called intramembranous particles. They are thought to be composed mostly of protein and can be arranged in a variety of patterns, linear or patch-like. Since the word mosaic reects the fact that various microdomains of membrane, even from dierent parts of the same eukaryotic cell, may have dierent patterns, as is found in the mosaic oors of ancient Roman villas, the term uid-mosaic model was put forward for membranes by Singer and Nicolson in 1982. This is now generally accepted as the most reasonable of the models.

The bilayer structure of the membrane permits the lateral motion of lipids and proteins, but not normally ipop movement, i.e. shifting from inside to outside or vice versa; this can occur only rarely, in the case of lipids with the aid of ippase enzymes. The membrane therefore is asymmetrical, with certain proteins facing the extracellular space or the outside environment, and others the internal cytoplasm. These tend to have special properties relating to the function they have, say, of recognition or anchoring, and may be peripheral or extrinsic, as distinct from integral or intrinsic, to the lipid bilayer. The anchors observed at the cytoplasmic surface tend to be the cytoskeletal elements, the microlaments, intermediate laments or the microtubules, as well as G proteins and other components of the second messenger signalling system. The external face has projecting carbohydrate moieties, which produce the glycocalyx of the plasma membrane. Here, too, reside receptor molecules that can be recognized by circulating hormones, antibodies or other molecules. Channels are also found straddling the plasma membrane. These may allow the inward or outward passage of ions such as Na 1 , K 1 , Cl 2 or Ca2 1 , and leakage or pumping of ions across the membrane may establish transmembrane resting potentials. These may be temporarily destroyed when action potentials occur in excitable membranes, such as those of nerve or muscle cells, with the transmission of a nervous impulse.

Internal Membranes and Subcellular Compartments: Organelles

The plasma membrane of all cells surrounds the cytosol or cytoplasm (cyto 5 cell) and separates each cell from the external environment. The internal compartmentalization of eukaryotic cells is also executed by membranes, which have the same basic bilayer structure as the plasma membrane. These divide up the large volume of cell cytoplasm into separate compartments, in which are concentrated specic substrates and enzymes for particular cellular activities. In this way, dierent cellular functions can occur at special sites with enhanced eciency. These compartments permit the vital functions of the cell to occur at specialized settings, and so are like the organs in the body of organisms. Since the cytoplasm surrounding the nucleus in the cell is called the cell body, these diminutive compartments have been termed organelles (Figure 1).

Endoplasmic reticulum
One of the most striking cellular organelles is the endoplasmic reticulum (ER), composed of numerous attened membranous cisternae lying throughout the cytoplasm; this is in continuity with the double nuclear envelope. It is often studded with ribosomes; if so, it is
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termed rough endoplasmic reticulum (RER); the RER makes proteins for export. If ribosomes are absent from the cisternae, it is called smooth endoplasmic reticulum (SER); SER is involved in lipid or steroid synthesis. The ribosomes synthesize the proteins required for cell structure and function by using information coding for the proteins structure from the linear DNA-like mRNA molecules. This mRNA, which emerges from the nucleus via nuclear pores, will not only be dierent for every protein but will be peculiar to each individual, because it reects the unique genetic make-up, or DNA structure, of that individual. The process of making mRNA from DNA is called transcription and occurs in the nucleus. Transfer RNA (tRNA) is also required during the process of protein synthesis, to bring the subunits of proteins, amino acids, into a linear array that is coded for by the mRNA. The ribosomal RNA (rRNA) is contained within the ribosomes, which act as the factory or sites in which the requisite components assemble together to synthesize the linear protein molecule. This process is termed translation and takes place in the cytoplasm. In eukaryotic cells this new protein molecule subsequently folds up within the cisternae of the RER, into which it has been inserted during the process of its synthesis by the ribosomes, to form the mature, functional form of the protein, destined for export. The protein enters the ER cisternae by a process commonly referred to as the signal hypothesis, whereby a terminal signal sequence of the protein being synthesized tells the cell that the protein should be inserted, via a pore through the RER membrane, into the ER cisternal space there. The linear protein nally folds up, inside the ER cisternae, into a three-dimensional functional form that is maintained, mainly by weak secondary forces, in the most thermodynamically stable conguration. Proteins can also be synthesized for use by the cell, without entering the ER cisternae at all. This is always the case in prokaryotic cells, which lack ER.

saccules receive the proteins from the RER at the forming face and then modify them by adding other components, such as carbohydrate moieties, and condensing them into mature dense granules. These become the secretory granules, which are pinched o, in a budding process, from the ends of the maturing face of the saccule stacks. These secretory products then move, probably along microtubules, to the surface of the cell, the plasma membrane, where they fuse their membrane with that of the surface, to undergo exocytosis. At this time the secretory product is released to the outside, and the secretory granular membrane becomes incorporated into that of the plasma membrane (see Figure 1).

Endosomes
The reverse of this process, endocytosis, takes place when materials are taken into the cell. Exogenous materials become surrounded by an area of plasma membrane, which phagocytoses them by taking them into the cytoplasm by rst forming a pit round them, and then budding it o internally. This membrane often includes a protein called clathrin, which makes the initial pit appear coated. This coat remains with the internalized membrane, now called the endosome, for a period of time before being recycled back to the plasma membrane.

Lysosomes
The endosomes are moved to the Golgi area, where their contents may be utilized or degraded by lysosomes. These are organelles synthesized by the maturing Golgi saccules, in an area sometimes referred to as the GERL. This region has a complex of enzymes peculiar to its activities, including the lytic enzymes which become incorporated into the forming, primary lysosomes. Once a primary lysosome has fused with an endosome and degraded its contents as far as is possible, it becomes a secondary lysosome. Lysosomes have been called suicide bags because their enzymatic contents, contained within the organelle membrane, are capable of degrading proteins, lipids, carbohydrates and nucleic acids. However, if, as sometimes happens, its enzymes are incapable of digesting all the endosomal contents, the lysosome is then called a residual body, as it now contains the indigestible residues of the ingested endosome. The molecules produced by the catabolic breakdown of the endosomal contents move out, through the lysosomes peripheral semipermeable membrane, into the ground cytoplasm to be reutilized. These secondary lysosomes tend to be found in the Golgi area of the cells, where they accumulate over time because they are incapable of themselves being extruded from the cell. Ageing cells, therefore, tend to have greater numbers of residual bodies. Collections of small vesicles enclosed within a membrane, termed multivesicular bodies, also

Golgi apparatus
The proteins synthesized in the ER are transported via membranous vesicles, to the so-called Golgi apparatus. This is a series of stacked saccules which often appear as dictyosomes, or scale-like bodies, under the light microscope. The structure was rst described as a network or reticulum in 1898 under the light microscope, by the Italian cytologist, Camillo Golgi, in nerve cells. Subsequent observers referred to these entities as Golgis bodies, Golgi complexes or the Golgi apparatus, by which terms it has been variously known ever since. Only with the advent of the electron microscope could its structure be denitely established, and it then became clear that Golgi bodies were stacks of attened saccules with associated vesicles and granules. They are like stacks of saucers with two distinct faces, a forming and a maturing face. These
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tend to congregate in the Golgi and lysosomal area; these may be a form of endosome.

Peroxisomes
Peroxisomes, another kind of organelle, may be found, especially in liver and kidney; these appear rather similar to lysosomes but they contain a special spectrum of enzymes d -amino acid oxidase, catalase and peroxidase. Like lysosomes, they are surrounded by a semipermeable membrane, but they possess a characteristic crystalline internum which is not to be found in lysosomes.

reaction, occurs in the stroma or internal space of the chloroplast. This is the pathway by which sugars are made from carbon dioxide and water. Like the mitochondria, these organelles also possess circular DNA and 70S ribosomes in their stromal space, and are thought to have evolved from symbiotic photosynthetic prokaryotes. The light reaction occurs in the thylakoid membranes, whereby photosystems I and II of the chlorophyll reactive centres capture the energy of sunlight and harness it to the production of reduced coenzymes and a proton gradient. Protons owing down the gradient lead to the production of the energy-rich ATP via CF0 (a proton channel) and CF1 (ATP synthase) in the chloroplast thylakoid membrane.

Mitochondria
Of comparable size, or perhaps a bit larger (about 23 mm) than the lysosomes, are the mitochondria. These are the organelles concerned with respiration. They possess both the components of the Krebs (or tricarboxylic acid) cycle and the proton pumps and ATP synthase, the enzyme that makes adenosine triphosphate (ATP), the source of cellular energy. The Krebs cycle in the mitochondrial matrix further breaks down the glucose, which has been initially partly degraded by the cytoplasmic glycolytic pathway, into smaller molecules. These drive the reduction of certain coenzymes which feed into an electron transport chain that forces protons to become concentrated in the space between inner and outer mitochondrial membranes. Mitochondria have two encompassing membranes, the inner of which is thrown into a series of folds called cristae. These cristae are studded with stalked particles, the stalk of which is called F0 and the head F1. The F0 is the proton channel across the inner mitochondrial membrane down which the hydrogen ions (protons) ow to drive the enzyme reaction which generates the energy-rich ATP, which is produced by the enzyme ATP synthase of the F1 head. In terms of its evolutionary development, the outer mitochondrial membrane is thought to have arisen from a primitive endocytotic event, when a prokaryotic cell was internalized by a eukaryotic cell and remained as a symbiont. Support for this contention comes from the fact that mitochondria are delimited by two membranes, and contain 70S ribosomes and circular, naked DNA, as do prokaryotic cells, within their matrix, or inner space. Their DNA codes for some, but not all, of their own component proteins, so mitochondria are only semiautonomous.

Cytoskeleton
Cells maintain their shape by a complex of internal structures jointly referred to as the cytoskeleton. This is composed of three major entities, the microtubules, the intermediate laments and the microlaments. These all feature linear cable-like structures, which are composed of alignments of subunits or monomers. They can be disassembled into their component monomers at any time and hence represent a very exible system. This is particularly apparent at cell division, when the tubular microtubules polymerize from individual monomers of tubulin and form the spindle, which is the structure to which the chromosomes become attached at cell division (mitosis). This is the time when each chromosome divides into two genetically identical daughter chromosomes, with one moving to each pole of the cell. The microtubules of the spindle disassemble after division has occurred, and are recycled back into the cytoplasmic microtubules and tubulin monomers of interphase. This process occurs only in eukaryotic cells, as prokaryotic cells do not have chromosomes which condense, nor do they possess a spindle. Microtubules, as the name suggests, are tiny tubules, 23 25 nm in diameter. Their basic subunit is a dumbbellshaped heterodimer of a- and b-tubulin. These polymerize into protolaments and there are usually 13 of these forming the wall of the microtubule around a hollow core. They not only comprise the spindle, but also form the 9 1 2 arrays in the motile cilia and agella, and are the cables along which proteins are transported from the nerve cell body of neurons to the terminal synapse, through the cytoplasmic axonal process. They appear to be associated with motor molecules such as dynein, kinesin or myosin, which empower the transport of, for example, vesicles along the microtubules of the axonal process. Similarly, microlaments are constructed of subunits of globular actin, called G-actin, which are linked into polymers called lamentous, or F-actin. This is the functional form which makes up the microlaments, 4
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Chloroplasts
Chloroplasts are organelles that are found only in the cells of plants. They are the basis of photosynthesis and are rather larger than mitochondria. They, too, have two outer membranes, as well as a third set of folded internal membranes, which make up the thylakoids, or stacked, chlorophyll-rich lamellae. The Calvin pathway, or dark

Cell Structure

6 nm in diameter, which lie as twin cables, intertwining in a helical array. These act as the devices to maintain the shape of cellular projections such as the microvilli of intestinal cells (Figure 2), which increase the cellular surface area dramatically in a highly advantageous way for absorption of nutritional molecules. They are also involved in cellular motility and, in muscle bres, make up a major subcomponent, actin, which lies alongside myosin, the motor molecule. In striated, or skeletal, muscle, as well as cardiac muscle, this is a highly ordered, close-packed array of the two molecules; this packing is less regular in smooth muscle. The two sets of laments, actin and myosin, slide past each other during muscle contraction, the myosin heads walking along the actin brils. This activity requires ATP as well as calcium (Ca2 1 ) ions; the latter are stored in cisternae of ER, ready for instant release when a muscular contraction is required. The Ca2 1 binds to another molecule, troponin, which shifts tropomyosin molecules, which in turn allow the myosin heads to interact with the actin, thereby activating the sliding lament

motion. Without ATP, the muscle laments cannot slide past each other, as the myosin heads cannot release and reattach to the actin, and rigor mortis ensues. The intermediate laments may dier chemically in dierent cell types but they all share certain similar structural characteristics. They are composed of varying numbers of brous subunits, which associate side by side into rope-like structures that possess enormous tensile strength. They are found around the inner nuclear envelope, as so-called nuclear lamins, as well as throughout the cell cytoplasm, anchoring on to the plasma membrane at specic junctures, the spot desmosomes, thereby acting as joints or junctions to hold adjacent cells together. These laments can accumulate as keratin in dead cells, persisting to form the hair and nails.

Multicellularity
Prokaryotic cells are always unicellular, but eukaryotic cells are the subunits of all multicellular organisms plants and animals. These cells are able to form multicellular systems because of their capacity to become dierentiated or specialized. This is possible because of their compartmentalization into organelles. Cells become specialized for dierent tasks depending on the arrangement of their internal compartments. The dierentiated state requires a reorganization or redistribution of certain of the major organelles, which will be dierent for each kind of specialized cell. Muscle cells require much energy, so have many ATP-generating mitochondria, while secretory cells, such as the pancreas, have extensive Golgi bodies, to help produce the requisite secretory products. This division of labour means that certain organs, made up of a certain kind of specialized cell, can be specially programmed for a particular function. The brain serves as a good example, as it is a collection of highly dierentiated neurons or nerve cells (surrounded by supportive glial cells), which synthesize and exchange chemical signals that permit nervous functioning, such as the capacity of animals to respond to their environment.

Nucleus

Cytoskeleton Intercellular junction Microvilli

(a)

Intercellular Junctions: Communication and Adhesion

Cells in a multicellular organism are linked together within organs by a variety of dierent intercellular junctions. These include: (1) adhering (adherens) junctions, such as the desmosomes, intermediate junctions and septate junctions (unique to the tissues of invertebrates); (2) the occluding junctions, such as the tight junctions; and (3) the communicating junctions, such as the gap junctions, which couple cells together. These are all variations on a theme of plasma membrane modication and serve to maintain the

(b)

Figure 2 The cytoskeleton of cells helps them to maintain different shapes: for example, (a) a nerve cell with an elongated axonal process; (b) an epithelial cell, in which the cytoskeletal components may help form the microvilli and the cell cell junctions that hold adjacent cells together and maintain cells in sheets or layers.

Cell Structure

integrity of tissues by holding adjacent cells together. Desmosomes are associated with underlying intermediate laments, and the intermediate and tight junctions with actin microlaments (Figure 2). Septate junctions, characterized by ladder-like septa straddling the intercellular cleft, seem to have associations with both actin and microtubules. Gap junctions appear to have no internal cytoskeletal attachments but they are responsible for cellcell communication, rather than merely holding adjacent cells together. They are formed by transmembrane subunits, connexons, which become precisely aligned in adjacent cells. Each connexon has a central pore, or channel, which is spatially associated with one of the adjacent cells connexons, so that ions and small molecules can be exchanged between cells via the channels. This allows the cells to communicate, as they can pass regulatory molecular morphogens from one cell to the other. The cells are then said to be coupled. They can become uncoupled by conditions such as high pH or calcium concentration, which cause the channels to become closed down. This appears to occur by a congurational change in the six hexameric subunits that make up each connexon. Plant cells, which possess thick cellulose cell walls, can only exchange information via plasmodesmata, which run between the cytoplasm of adjacent cells. These are tiny cytoplasmic passageways through the cellulose walls that carry a minute strand of ER from one cell to the next, through which molecules may move.

Communication
The developing multicellular organism becomes divided into groups of cells cooperating as tissues. These must selectively adhere to one another to remain as organs, and their component cells must also be able to communicate with each other if division of labour is to occur eectively. This they do by a number of devices, of which one of the most important is the nervous system, where signals are sent by chemical neurotransmitters from one neuron to other cells. Hormones, protein or steroid, also have profound chemical eects on developmental processes, including the acquisition of secondary sexual characteristics, by activating dierent genes in the DNA. Circulating hormones may also trigger secondary signalling pathways. Local hormones play important roles in adjacent cellular activity, as may other chemicals that operate by chemotaxis or via chemical attractants. Signalling via cell surface molecules also occurs in the immune system, which is based on cellular signals and responses that activate special B and T cells in the lymphoid system, using either humoral or cellmediated mechanisms. This is important in enabling the organism to survive infection. Growth factors and cellular adhesion molecules may also aect the patterns of dierentiation of cells in the formation, and then the maintenance, of organs. This may involve the assembly of the cellcell junctions, described earlier, which keep the adjacent cells associated together in particular arrangements. The interplay of chemical signals between the cells of the same or dierent organs produces an orchestration of cellular activity resulting in a successful, functional organism. The healthy organism, therefore, is dependent on the eective functioning of the cells that make up its organs.

Differentiation
All new individuals arise from fertilized eggs, or zygotes, which then divide many times thereafter to produce embryos, then adults. The egg cell cytoplasm contains an organized system of determinants which assign cells to dierent developmental pathways. These cytoplasmic dierences require the zygote nuclear gene expression. This selective activation and expression of specic genes leads to cell and tissue dierentiation. The details of the embryonic pattern are lled in by mechanisms which sort cells into particular pathways of dierentiation by their relative position in the developing organism. Groups of cells generate positional information, perhaps due to gradients of diusible substances within boundaries in tissues, leading to pattern formation that is seen, for example, in limb formation. Genetic studies have led to the discovery of homeotic (HOX) genes (master regulatory genes), which determine the mainstream developmental pathways of the dierent appendages (e.g. arms versus legs) or units of the body plan of organisms. Developmental cell biology is rapidly emerging as the branch of the subject producing some of the most exciting revelations about the way the complex pattern of dierentiated tissues becomes organized.

Further Reading
Alberts B, Bray D, Lewis J et al. (1994) Molecular Biology of the Cell, 3rd edn. New York: Garland. Alberts B, Bray D, Johnson A et al. (1998) Essential Cell Biology: An Introduction to the Molecular Biology of the Cell. New York: Garland. Darnell J, Lodish H and Baltimore D (1990) Molecular Cell Biology. New York: Scientic American. Fawcett D (1981) An Atlas of Fine Structure: The Cell. New York: Saunders. Holtzman E and Noviko AB (1984) Cells and Organelles. New York: Saunders. Judson HF (1996) The Eighth Day of Creation: Makers of the Revolution in Biology. Cold Spring Harbor: Cold Spring Harbor Laboratory Press. Lewin B (1983) Genes. New York: Wiley. Rensberger B (1996) Life Itself: Explaining the Realm of the Living Cell. Oxford: Oxford University Press. Smith CA and Wood EJ (1996) Cell Biology. London: Chapman and Hall. Stryer L (1981) Biochemistry. New York: Freeman.