II. FORM AND FUNCTION IN ONTOGENY
There is evidence (1) that the issues of the brain and the rest of the body constitute an organic, interdependent unit; and (2) that organisms are not programmed for their behavior by an ex-machina force, but instead they develop a program ontogenetically together with nervous and nonnervous tissues.
(1) Mutual influence in the development of Nervous and Other Tissue
Let us first consider the developmental relationship between nervous and other tissue. Our discussion can be divided into (a) metabolic or trophic relationships and (b) nonmetabolic, particularly mechanical relationhships.
(a) Trophic Relationships. Nervous tissue stands in an intimate relationship to other tissue anatomically contiguous to it. This is shown most clearly by the essential role played by nerves in the process of regeneration. There are a number of studies available which indicate that regeneration of an entire limb in lower vertebrates (fish, lizards, urodele, salamander, larval anuran, and postmetamorphic frog) and probably also in invertebrates is dependent on the presence of nerves in the amputated stump (Singer, 1959, Gutmann, 1964).
In a series of experiments by Schotté and Butler (1944), Singer (1947), and their students, and Nicholas (1949), it has been shown that an amputated limb will not regenerate unless an intact nerve is either present in the remaining stump from the beginning or is transplanted into the cut surface by autograft (however, see Thornton and Steen, 1962). Morphogenesis, that is, an orderly sequence of tissue differentiation and development of the lost appendage, will not ordinarily take place in the absence of living nervous issue during the very first stage of regeneration. If all nerves are removed form this stump during the earliest period, mitotic activity is dramatically slowed down; eventually some small amount of connective tissue, cartilage, and muscle may form in a disorderly nonfunctional fashion, giving a shriveled and shapeless appearance to the stump. If viable nervous tissue is not present from the start of the amputation but brought into the so-called blastema shortly afterward, regeneration takes place but the regenerate limb is poorly developed. The nerve need not be present throughout the entire period of regeneration; once the limb has begun to grow and tissues are sufficiently differentiated, the nerve may be removed without impariment of the morphegenetic potency acquired by these tissues during their earliest stage of formation. Singer (1974) has shown that it does not matter for regeneration what type of nerve, whether motor, sensory, or autonomic, is present in the blastema. It is merely the amount of nervous tissue present that controls the regenerative possibilities. Apparently a product of nerve-cell metabolism induces morphogenesis in the blastema.
These studies leave many questions about the biochemistry of embryology and growth unanswered; yet they do give us a glimpse of the complete interdependence and the natural integration of different tissues in the animal body. This impression is further strengthened if we consider some of the other trophic relationships that nerves have to peripheral tissue (for instance, the well-known fact of denervation atrophy). If the axon of a motor neuron is cut, the portion distal of the cut will die promptly, presumably because of its separation from its source of supply of vital substances (Gerard, 1950). But this is not the extent of the degenerative changes following the section of a motor nerve. The muscle innervated by the nerve will also undergo dystrophic changes with an extremely characteristic histological appearance. The loss of muscle substance is not due to a “functional” disturbance, such as the inhibition of nerve impulse transmission (Hamburger & Levi-Montalcini, 1950) nor due to disuse of the muscle; the muscle cannot be saved from atrophy by passive exercise. Indeed, the metabolic interdependence of nonnervous, peripheral tissue and nervous tissue is proven by the fact that the nerves themselves must have anatomic continuity with muscles for proper metabolic function. Severance of nerve from muscle will induce retrograde changes in the body of the neuron (the soma), known as chromatolysis, which is a sign of dysfunction.
Perhaps the most striking evidence for the subtle but definite interdependence of peripheral structures and the central nervous system is provided by the stunted growth resulting from large cerebro-hemispheric and specifically parietal lobe lesions in the neonate human. This phenomenon was described by Macdonald Critchley (1955) and has been generally known to occur in connection with a condition called infantile hemiplegia. The stunting of the body side contralateral to the brain lesion occurs both in congenital and in acquired infantile hemiplegia and is not due to disuse, first because all tissues in the extremities involved are equally affected and second, because the arrest of growth starts at birth in the congenital cases, that is, before either the affected or the unaffected side is actively being used (Holt, 1961). These cases are even more interesting in the present context than the denervation atrohy, because here we see a relation between the highest level of the central nervous system and nonnervous structures of the periphery. Because the cells of the cerebral cortex are separated from those on the periphery by several internuncial neurons, there is an indication of a very subtle control that the higher centers of the central nervous system appear to exe3rcise upon the development of the body as a whole.
(b) Mechanical Relationships. In addition to the metabolic influences between nervous tissue and other tissue, morphogenesis is controlled by several other factors, some of which are indirectly related to neurophysiology. A good illustration is furnished by the mechanical forces exerted upon growing tissue, particularly bone, which stimulate cell division in certain directions. As muscles are innervated and begin to function, they exert a pull upon the boned to which they are attached and thus help shape the internal structure of this tissue.
It has often been noted (and, unfortunately, frequently been emphasized out of all proportion to its true importance) that the architecture of certain organs is ideally suited to their function. An excellent example of this was provided by D’Arcy Thompson (1942) who wrote, “In all the mechanical side of anatomy nothing can be more beautiful than the construction of a vulture’s metacarpal bone. The engineer sees in it a perfect Warren’s truss, just such a one as is often used for a main rib in an aeroplane.” The fundamental schema of the shape of individual bones and the skeleton as a whole are undoubtedly the result of evolutionary processes including selection and adaptation on a phylogenetic rather than an ontogenetic scale (Hackenbroch, 1957-1962). However, the actual realization of what is only potentially present in the fertilized egg is largely dependent upon factors which are active during ontogenesis. This is vest illustrated by the development of the internal structure of bones. In 1866, a Swiss engineer, Culmann, noted that the internal trusses in the head of a human femur, anatomically known as trabeculae, were oriented in exactly the direction of the lines of maximum internal stress. He drew a diagram of a curved rod showing the lines of stress resulting from the application of a load from above (Fig. 1.1a). The model somewhat resembled the head of a derrick which he had just designed, and it is therefore referred to as a crane’s head. It bears a striking similarity to a section of the head of the femur (Fig. 1.1c). Culmann’s idea gave rise to J. Wolff’s famous theory expressed in his monograph on The Law of Bone Transformation (1870), according to which every change in the function of a bone produces changes in its trabecular architecture and external form in conformity with mathematical, static laws. The theory has since been criticized (Küntsher, 1934, 1936), modified (Murray, 1936), and elaborated upon (Evans, 1955, 1957, 1960; Carey, 1929). However, the idea is widely accepted today that muscles, through the tonus already present on early embryonic life, exert essential forces upon the growing bone. These pressures, together with those produced by differential growth of various parts of the embryo, result in stresses and strains which are the prerequisite stimuli for proper bone formation.