Molecular Biology of the Cell - Volume 3 - Alberts B., Bray D., Lewis J., Raff M., Roberts K., Watson J. 1994

From Cells to Multicellular Organisms
Maintenance of Normal Tissue Organization
Maintenance of the Differentiated State

Although body Tissues differ from one another in many respects, all of them require certain basic conditions, typically met by a combination of different Cell types. This is illustrated for Skin in Fig. 17-1. Above all, tissues need mechanical strength, which is very often provided by the Extracellular matrix (see Section 14.2) secreted by fibroblasts. In addition, almost all tissues require a Blood supply to deliver nutrients and remove waste products; they are therefore permeated by Blood Vessels lined with endothelial Cells. Likewise, most tissues are innervated, meaning they contain nerve cell (neuron) axons sheathed in Schwann cells. Macrophages are also generally present to clear away dead cell debris and excess matrix, alongside lymphocytes and other white Blood Cells designed to fight infection. Sometimes, tissues may house melanocytes, which provide protective or decorative pigmentation. Most of these auxiliary cells, which play a supportive role relative to the tissue's primary function, originate outside the tissue and invade it either early in development (endothelial cells, Neurons, Schwann cells, and melanocytes—see Section 16.6.5) or throughout life (macrophages and other white blood cells). This complex support apparatus is essential for sustaining the main specialized cells of a given tissue, such as contractile cells in Muscle, secretory cells in a gland, or blood-forming cells in Bone Marrow.

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Fig. 17-1. Structure OF THE Skin. The outer Epithelial Tissue (epidermis) and the underlying Connective Tissue (dense dermis, which is processed into "leather," with looser fatty tissue deeper down) are shown. Each tissue consists of various cell types. The dermis and subcutaneous layer are richly supplied with blood Vessels and nerves. Some nerve fibers also extend into the epidermis.

Thus, almost every tissue is a complex mixture of many cell types that, while sharing the same environment, nonetheless maintain their distinct identities. Moreover, the Organization of this cell mixture must be preserved even though, in most adult tissues, cells are continually dying and being replaced by new ones. This maintenance of tissue form and function is made possible largely by two fundamental cellular properties. Cell memory (see Section 10.3) enables differentiated cells to autonomously maintain their characteristic specialization and pass it on to daughter cells. At the same time, differentiated cells of any type constantly "sense" their surroundings and adjust their proliferation rate to match the circumstances. Intracellular mechanisms presumably responsible for cell memory were discussed in Chapter 10, while the ways cells respond to external signals were examined in Chapter 12. Here, in this introductory section concerning cell behavior within tissues, we will briefly review some evidence On the Stability and heritability of the differentiated state and examine the extent to which this state can be modified by environmental influences.

17.1.1. Most Differentiated Cells Generally Retain Their Specific Characteristics Even in a New Environment [2]

Experiments on tissue cultures demonstrate that even when cells are deprived of their normal environment, both the cells themselves and their progeny typically continue to follow their intrinsic initial "instructions." Consider, for example, the epithelial cells that form the pigmented layer of the retina (Fig. 17-2). Because the specialization of these cells is manifested by The production of dark brown melanin granules, monitoring their state of differentiation is straightforward. Pigment epithelial cells can be isolated from the chick embryo retina and grown in culture, where they proliferate and form clones. Single cells taken from these clones invariably give rise to subcultures consisting of similar pigment epithelial cells. In this way, the differentiated state can be maintained through more than 50 cell generations.

However, cell behavior also depends to some extent on environmental conditions. In certain media or at excessive culture densities, cells survive but synthesize little or no pigment. Yet even when deprived of the opportunity to express their specialization, these cells remain determined as pigment cells: once returned to more suitable conditions, they resume pigment production. There is one well-known exception to this rule: under specific conditions, these cells will transdifferentiate into lens cells; however, no Changes in the culture medium or growth conditions can convert them into, say, blood, Liver, or Heart cells.

Not only in culture, but also in the intact Organism, almost all differentiated cells behave as though their major features were irreversibly determined during development. For instance, epidermal cells remain epidermal even in the most inappropriate environment: if a suspension of dissociated epidermal cells is prepared from rat tail skin and injected under the Kidney capsule, the cells will grow there, forming epidermal cysts containing Hair follicles and Sebaceous Glands, just like in the skin on the body surface.

17.1.2. The Differentiated State Can Be Modified by the Cellular Environment [1, 3]

Although radical cellular transformations are generally impossible, the character of many differentiated cells can adapt to some degree to environmental conditions. The allowable changes in cells are mainly modulations of the differentiated status—that is, reversible interconversions of closely related cell phenotypes. For example, liver cells decrease or increase the synthesis of certain Enzymes (by altering the amounts of the corresponding mRNAs) depending on the concentration of the steroid hormone hydrocortisone. Muscle cells also modify their pattern of Gene Expression IN response to the level of stimulation they receive (Sections 17.6.2 and 19.8.4). Fibroblasts and related cells—the CONNECTIVE TISSUE CELL family—represent a special case. These cells possess exceptional adaptability and can undergo a variety of interconversions; for example, fibroblasts can reversibly transform into Cartilage cells. Such transformations are important in wound and fracture healing, as well as in other pathological processes. These are discussed in more detail in Section 17.7, which shows how these transformations are regulated by cell shape, the extracellular matrix, and diffusing signaling molecules. Nevertheless, even such modifications of differentiated cells are possible only within narrow limits: the altered cell remains a member of the connective tissue family.

Fig. 17-2. Development of the vertebrate eye. The eye retina develops from the optic vesicle—an epithelial protrusion of the neural tube in the Forebrain region. A. The neuroepithelium contacts the ectoderm covering the outside of the HEAD. B. This contact induces the invagination of the ectoderm, followed by The formation of the lens. Simultaneously, the wall of the optic vesicle facing the epidermis indents inward, and the vesicle takes on a cup shape. C. The layer of the optic cup closest to the lens differentiates into the neural retina, which includes photoreceptors and the neurons that transmit sensory impulses to the Brain (see Fig. 17-6). The other layer differentiates into the retinal pigment epithelium. Its cells, densely packed with melanin granules, form a darkened shelter for the photoreceptor system which, much like the black interior of a camera, reduces The amount of scattered light.

17.1.3. Some Structures Are Maintained Through the Continuous Interaction of Their Parts: An Example of Taste Buds and Their Nerves [4]

Taste buds serve as another unusual example of a differentiation state that depends on continuous cell-cell interactions. These tiny structures, through which we perceive sweet, sour, salty, and bitter tastes, form mainly in the epithelium of the upper surface of the Tongue. Each bud consists of about fifty cells that are easily distinguished from surrounding epithelial cells by their shape (Fig. 17-3). The elongated taste bud cells, arranged like staves in a barrel, extend through the entire thickness of the epithelium, forming a small opening (the taste pore) that opens to the exterior. It is believed that molecules of taste-producing substances must penetrate inside through this pore. At least Two Types of cells—pale and dark—can be distinguished in a taste bud, among which are cells acting as taste receptors. Sensory signals are transmitted to the brain via nerve fibers that penetrate the taste bud and terminate on its cells. If these nerve fibers are severed, the taste buds completely disappear. Regeneration of the nerve fibers causes the differentiated state of the epithelial cells to change, forming new taste buds. Taste buds can even be induced to form in areas of the epithelium where they do not normally occur, such as the underside of the tongue, by culturing a piece of epithelium in vitro together with the appropriate sensory ganglion to innervate it. However, despite such Examples, most adult tissues consist of a set of clearly defined, irreversibly determined cell types. Their numbers and spatial relationships must be maintained throughout life by mechanisms that do not require The conversion of one cell type into another.

Fig. 17-3. Schematic diagram of a taste bud.

Summary

Most differentiated cells in adult tissues will retain their specific character even in a new environment. Although differentiated states are generally stable and irreversible, even highly specialized cells can alter their properties within certain limits when the environment changes. Particularly significant transformations occur within the connective tissue cell family, which includes fibroblasts and cartilage cells. Taste buds provide another striking example of how a state of differentiation can depend on ongoing cell-cell interactions: the specialized taste bud cells completely disappear after nerve transection and reappear upon re-innervation.