The development of a new organism from a single cell, the fertilized egg, is a remarkable feat of nature that has long fascinated biologists and non-biologists alike. During the first 4 weeks of human development the seemingly homogenous egg is transformed into an EMBRYO. As development proceeds further, the primitive elements of all the major body organ systems become precisely organized with respect to each other. By now, the embryo acquires an unmistakably human appearance and is known instead as a FOETUS. Subsequent development builds on this foundation, and largely concerns the growth and elaboration of these structures into the organs proper.
During the earliest stages of development, cells in different regions of the embryo acquire their developmental identity or fate. This involves a number of distinct but nonetheless integrated processes, and many concepts are simply illustrated by considering the development of the limbs. All fingers, for example, are comprised of the same cell types such as bone, cartilage and muscle, but each individual finger has a unique shape and forms in the correct position in the embryonic limb bud. How a finger acquires its individual positional identity is a problem of regional specification or pattern formation. This process controls, and can be distinguished from, cell DIFFERENTIATION, which concerns how precursor cells become restricted in their fates by activating cell type-specific gene expression pathways (see GENE). Pattern formation is directed by MORPHOGENS. These are molecules that impart positional information, such that different embryonic structures are induced to differentiate down specific pathways by different morphogen concentrations. For the limb, a signalling centre on one side of the early limb bud secretes the morphogen, a protein known as SONIC HEDGEHOG (shh), and this diffuses within the bud (see SECRETION and DIFFUSION). As a result, a concentration gradient of shh is established within the bud, with the highest concentration at the site of shh secretion. Distinct digits are then formed as cells differentiate at different positions in the gradient, a little finger appearing at high morphogen concentrations and a thumb at low concentrations. Much of early development, including that of the nervous system, is concerned with such pattern-forming mechanisms. The related concept of MORPHOGENESIS refers to the physical and mechanical events that govern how cells and tissues move in the embryo and mould the final shape of the various organs.
Development also involves a hierarchy of decisions whereby cells become committed to ever more restricted fates, and this involves two major mechanisms. CYTOPLASMIC DETERMINANTS refer to substances localized to specific regions of the egg CYTOPLASM which are then distributed asymmetrically in the dividing embryonic cells to influence their subsequent fates, a strategy seen in the development of invertebrate embryos. By contrast, vertebrate embryos generally use INDUCTION, whereby cells in one region of the embryo are directed by external signals (such as morphogens) produced by cells in other regions. The earliest commitment after fertilization is to a particular germ layer, whether ECTODERM (neural tissue and skin), MESODERM (such as muscle, heart, kidney, liver, blood and bone) or ENDODERM (for example, intestine). Experiments using amphibian embryos have shown that early mesoderm is induced from tissue that would otherwise make ectoderm, by proteins (such as members of the FIBROBLAST GROWTH FACTOR family and transforming growth factor beta superfamily) emanating from the endoderm.
A critical event after mesoderm induction is GASTRULATION (once defined as a life-event of greater importance than birth, marriage or death). During gastrulation, the mesoderm undergoes a complex series of movements, extending and migrating between the ectoderm and endoderm to generate the definitive positions of the three germ layers. In vertebrates this process is coordinated by a special structure called the organizer (or node) of the PRIMITIVE STREAK, and this is responsible for at least three overlapping activities. It influences subsequent neural development (see NEURODEVELOPMENT) by inducing the overlying ectoderm to form neural tissue (neural induction), and it directs the establishment of the definitive head-tail and dorsal-ventral axes.
One of the most exciting insights of modern developmental biology has come through the study of genes that are responsible for giving body segments their individual identities along the head-tail axis of the fruit fly (Drosophila) embryo, for example distinguishing thoracic, wing-bearing segments from abdominal segments. These HOMEOTIC SELECTOR GENES have their counterparts in vertebrate embryos, and it is striking that their expression patterns and function show a close correspondence in insects and vertebrates (see NEURODEVELOPMENT). Many other genetic signalling pathways that regulate embryonic development have also turned out to be conserved between vertebrates and invertebrates. The differences between organisms presumably lie in the details of the deployment of these pathways, and we are still a long way from understanding how the human brain, in particular, comes to be different from that, say, of a rat.
ROGER J.KEYNES
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