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First molar tooth germs consisting of dental organ, dental papilla and dental follicle were dissected from one-day old mice and transplanted subcutaneously into young adult animals of the same strain. Three to four weeks after implantation the host animals were sacrificed and the transplants harvested. The transplants were prepared for either routine histological examination or for electron microscopy. Forty tooth germs continued development with the formation of a periodontium consisting of cement, periodontal ligament and bone. Electron microscopical examination of this material demonstrated the presence of lymphocytes in association with the subcutaneous bone and thereby suggested the origin of the bone from donor tissue.

Curves showing the growth of lacteal and permanent teeth in anthropomorphic species from Asia, from Africa and in Man were drawn after orientation of the skull according to the vestibular axes. They combine, in an “absolute” movement, part of the teeth with regard to the maxillary bones and their relation to the system of reference axes. Several points arise, which add to the general phenomena of backward movement and to the phylogenic reduction of the splanchnocranium.

Summary This investigation was carried out in order to get further information onthe mineralized dental tissues. Two young normal dogs were injected, one with Na 2 S 35 O 4 , the other with Ca 45 Cl 2 . From selected parts of the lower jaws thin ground sections were prepared. These sections were studied by means of a combination of autoradiographic and microradiographic techniques. The autoradiographs revealed an uptake of both Ca 45 and S 35 in essentially the same locations of the bone and tooth tissues. There was thus a high uptake of isotopes in the periosteal areas and in young osteons and certain areas of the cancellous bone. In the deciduous teeth the labelling was most pronounced along the pulpo-dentinal border. In the tooth germs there was a high uptake of both isotopes along the pulpo-dentinal border in the same area. There was also a labelling along the enamel surface. In certain tooth germs, where the microradiographs indicated a high mineralization in the cusp tips, there was a diffuse labelling throughout the whole breadth of the enamel. These findings were interpreted as an expression of a secondary mineralization. The uptake of S 35 differed in certain respects from that of Ca 45 . In the tooth germs there was thus an uptake of S 35 along the dentino-enamel junction, and in the soft tissues, especially in the pulps of the tooth germs, there was also a marked labelling of S 35 only. Further, the labelling at the pulpodentinal border showed features differing from the autoradiographs obtained with Ca 45 . Thus the uptake of S 35 at this site was concentrated in two closely adjacent bands. It was concluded that the uptake of Ca 45 took place in the mineralized constituents of the tissues. However, as regards S 35 , one part was probably incorporated in the crystal lattice of the minerals, another being deposited with the organic matrix, presumably as mucopolysaccharides containing ester sulfuric acid. This latter conclusion refers to the uptake along the pulpo-dentinal border.

Incidence of the so-called thalidomide baby has created a gravest social problem and it is typical of the collateral effect to be derived from various new drugs which have been more or less fashionable in recent years. We were fortunate enough to obtain for our investigatory purposes the jaws from a thalidomide-baby (Contergan baby, to use the term coined by LENZ [1]) which had been born of a woman who had taken a large dosage of thalidomide preparations in the course of her pregnancy. The present paper is concerned with some of its interesting findings pathologically examined.

The fine structural pattern of the incisor enamel of rats, mice and guinea-pigs was examined in normal (control) and in fluorosed and transplanted teeth. The enamel formed under the influence of NaF injections showed a subtle change in direction of the fibres and crystallites in the defect lines. The enamel formed in tooth germs which had developed in the brain had lost all traces of the normal “plywood” pattern. Genetic factors must act indirectly on enamel structure, via the influence of spatial conditions in the jaw-bone alveoli.

The incisor regions of two pouch-young stages of Isoodon macrourus, snoutocciput lengths 2.2 and 3.5 cm, were sectioned transversely, and the tooth germs and dental laminae were graphically reconstructed. I2 was lingually positioned to I3 in both stages. As, in the younger state, I3 and not I2 had retained a connection to the dental lamina, it is concluded that I2 can not originally have been a successor of I3. It is concluded that I5 in Peramelidae originates later than the canines and the other incisors, but belongs to the same dentition as these teeth. In both stages, there was a well-defined terminal enlargement on the dental lamina lingual to I1. The appearance and dimensions of this structure closely resembled that of tooth germs in the early cap-stage. This indicates that the residual dental lamina may represent a separate dentition.

On the basis of a material consisting of primordia of deciduous teeth from 17 human foetuses and tooth germs from 20 newborn mice and 4 mouse foetuses, the histochemical distribution of succinic dehydrogenase, LDH, BDH, glucose-6-phosphate-dehydrogenase, NADH2 cytochrome C reductase, and NADPH2 diaphorase was studied.

Reduction in size of the jaws during hominid evolution has been accompanied by an overall reduction of tooth size, but the degree of reduction varies from one tooth to another in a definite pattern. Within each morphological class (incisors, premolars and molars) the later a tooth develops the more it has been reduced. Similar relationships between developmental timing and degree of reduction may have been commonplace during the evolution of mammalian dentitions in general (Ziegler, 1971). However, later developing teeth tend to have lower heritabilities for tooth size than their earlier developing neighbours (Lundstrom, 1948; Hunter, 1959; Bader, 1965; Bader and Lehmann, 1965; Sofaer et al., 1971a). Thus there appears to be an association between lower heritability and more rapid evolutionary change. It is possible that this is the result of selection that has acted directly on the later developing teeth of each class causing a reduction of genetic variation. It is perhaps more logical to consider that the bulk of any selection acts on each morphological class as a whole rather than differentially on the individual teeth of which it is composed. In the absence of direct differential selection on members of the same class the association between lower heritability and more rapid evolutionary change can be explained if it is assumed that some proportion of the reduction that has taken place in the dentition has been secondary to skeletal reduction, through selection for harmony between size of teeth and size of jaws. In such a system the primary reduction of jaw size might be expected to have resulted in restriction of the developing teeth, with consequent compensatory interaction between adjacent tooth germs due to competition for requirements necessary for growth. That is, if for some reason a tooth which developed early was larger than normal, then its later developing neighbour would have tended to be smaller than normal, and vice versa. There is evidence to suggest that this kind of compensatory interaction occurs in contemporary populations of both man and experimental animals (Griineberg, 1951; Grewal, 1962; Van Valen, 1962; Gould and Garwood, 1969; Sofaer, 1969a; Sofaer et al., 1971a; Sofaer et al., 1971b). In order to explain differential tooth reduction in terms of selection for harmony between tooth size and jaw size, it is necessary to show that genotypes with the potential to produce relatively large early developing teeth and small late developing teeth are favoured over those with the potential to produce relatively small early and large late teeth. A simple example of how compensatory interaction under conditions of local restriction can produce this result has already been proposed (Sofaer et al., 1971a). The purpose of the present paper is to put forward a generalised model and to discuss the patterns of variation that might be expected in contemporary populations if the model were valid.

Allogeneic skin grafts transplanted on recipients presensitized with allogeneic tooth germs showed an accelerated rejection pattern. Apparently, developing teeth contain antigens of the major histocompatibility system, and these antigens are able to elicit a strong allograft reaction in the recipient.

Repeated doses of fluoride over 2 days produced marked alterations in the fine structure of ameloblasts from tooth germs of young rats: large confluent distensions of the endoplasmic reticulum and swelling of isolated mitochondria. The appearance was similar to the documented material on initial degenerative changes in hepatocytes by a variety of other toxic agents. The possible role of these changes in the production of enamel fluorosis is discussed.

An infant girl was found to have partly formed deciduous lower central incisors erupted at birth. The enamel and dentine shell of one incisor was dislodged a few days after birth, and the other was removed three to four weeks later. By the age of 13 weeks two tumorlike masses had formed in the lower central incisor region. Histologic examination showed that these masses resulted from the continued growth of the dentine papillae, with the formation of both regular and irregular dentine and continued activity of part of Hertwig's sheath. The findings in this patient were very like those derived from tissue culture experiments with rat tooth germs and provide further confirmation that the results of experiments with animal tissues on the differentiation and growth of the dentine papilla apply also to man.

Newborn rats were exposed intermittently to oxygen at high pressure (93 psig) 15 times for a period of eight days. Growth of the tooth germs was the same as that of the control rats in air at atmospheric pressure, with the exception of the enamel and dentin layers, which grew less. The width of the tooth germ of rats exposed to oxygen at atmospheric pressure increased.

Lactating dams with 8 suckling pups were fed either a 6 or 20 per cent protein diet from the birth of the pups to day 15. Pups were divided into caffeine and non-caffeine groups and, every other day between days 3 and 13, were either intubated with caffeine ( 1 mg 100 g body wt) dissolved in 0.1 ml physiological saline solution, or 0.1 ml saline solution as a control. At day 15, the weight of incisors and molar germs, hydroxyproline content, collagen synthesis and calcium contents were determined. Nutritional factors exercised consistent effects on all the parameters, but effects attributable to caffeine intubation were minor. There was lower molar weight in the 20 per cent protein group with caffeine, and collagen synthesis of incisor and molar germs in the caffeine and non-caffeine animals in the 6 and 20 per cent group were different. These parameters showed a significant interaction between nutrition and caffeine. Thus the direct administration of a small amount of caffeine to newborns causes only slight effects on tooth-germ development under some nutritional conditions.

The effect of protein-energy malnutrition on the growth of molar and incisor tooth germs was studied. Significant differences were found between control and malnourished groups in the weights and calcium contents of both tooth germs. The data point to the importance of the effect of nutrient deficiency on the critical growth period of an oral structure.

Transmission electron microscopy of tooth germs in early stages of development revealed that cell processes from ameloblasts and odontoblasts come into proximity, appearing sometimes closely juxtaposed. These regions of approximation do not form any well-known type of junction but are possibly a manifestation of some form of epithelial-mesenchymal interaction.

Biosynthesis of enamel protein was investigated by incubating bovine tooth germs with 3H-proline containing medium. The radioactivity was incorporated into two protein fractions: one had a molecular weight of about 25,000, being secreted from the ame.'oblast to the enamel matrix, another having a higher molecular weight was supposed to be a cell associated protein.

A micro-PIGE (Proton-Induced gamma-ray Emission) technique based on the delayed 5/2+----1/2+ nuclear transition of fluorine (E gamma = 197 keV, t1/2 = 87 ns) emitted after 19F(p,p', gamma)19F reaction was used to detect and study the distribution of fluorine in the developing enamel organ during pre-eruptive stages, i.e., the transitional to early maturation stages of enamel formation in neonatal hamsters administered a single IP dose of sodium fluoride (20 mg NaF/kg body weight). The aforementioned nuclear reaction is unique for fluorine, and therefore detection of gamma-rays emanating from this reaction in a biological specimen implies a positive identification of fluorine at that particular site. Calcium and phosphorus X-rays were also recorded and used as parameters for assessment of the relationship between the degree of mineralization and fluoride incorporation into the enamel organ. The highest fluorine concentration in the enamel organ was recorded in the dentin near the dentin-enamel junction (DEJ). In the enamel, the highest concentration of fluorine was found to be associated with the more mature areas of the enamel near the DEJ, but gradually decreased in the direction of the enamel surface. Fluorine was not detected in the control germs. These results suggest that administration of fluoride in high doses during the pre-eruptive stages of enamel formation leads to incorporation of the ion into the forming dentin and enamel mineral, and that the enamel matrix does not seem to bind fluoride avidly.

Real impaction and submersion of deciduous molar teeth are presented in patients of different ages. Various forms of submersion such as secondary infraocclusion and complete submersion are differentiated. In addition, most of these cases showed permanent abnormalities, e.g. hypodontia (partial anodontia) and impaction. The authors believe that these abnormalities can be regarded as already determined at an embryonal stage. They may be the consequence of an abnormal situation of the tooth germs or, on the other hand, an originally decreased inclination to normal eruption of these teeth. Mechanical pressure of adjacent teeth and ankylosis can be regarded as a secondary cause in the irregular formation of deciduous molar teeth.

Single-cell suspensions of dissociated rat molar tooth germs were grown in vitro in modified Rose chambers and in vivo in diffusion chambers implanted subcutaneously in host rats. Using phase contrast microscopy and time lapse cinemicrophotography, the cells were observed in vitro to form aggregates consisting of groups of mesenchyme-like and epithelium-like cells. In material from the in vivo study, it was also observed that the dissociated cells re-aggregated to form sheets of epithelial and mesenchymal cells and sometimes to form more organized structures resembling epithelial cell rests of Malassez. Storage of the tooth germs at −196 °C for 3 weeks prior to trypsinization aided dissociation and appeared to have no deleterious effect on the subsequent viability and behaviour of the stored cells.

Mineralization and matrix formation are closely related processes in the growth and development of both incisor and molar tooth germs. Addition of ascorbic acid does not affect in vitro collagen synthesis of tooth germs from protein-energy malnourished rats.

Twins and families were investigated to obtain information about inheritance of tooth-crown size. Sixty twin pairs and 100 families were examined using four methods of estimation. The results suggest genetically controlled interactions between tooth germs during their formation. A hypothetical model of odontogenesis is presented.

Trace elements can influence dental health, possibly by altering tooth resistance during preeruptive development. Therefore, it was investigated whether lead and fluoride would be incorporated into the calcifying matrices or the cellular parts of tooth germs in vitro. Using laser microprobe mass analysis, the localization of lead and fluoride was studied in the different layers or tooth germs that had been cultured in a medium to which PbCl2 of NaF had been added in different concentrations. Both elements could only be detected in the dentine layer. Hence, the enamel organ in the secretory stage of tooth development excludes lead and fluoride from the enamel, even when enamel formation by the ameloblasts is visibly disturbed. Furthermore, there seemed to be a process of saturation in the accumulation of lead and fluoride in the dentine.

The anatomy of the teeth and tooth-related nerves in the lower jaw was examined in the cichlid Tilapia mariae. This was done in order to establish a basis for studies on dental neuroplasticity in a polyphyodont vertebrate. The region of interest was explored in specimens fixed by glutaraldehyde perfusion, and by using X-ray photography, maceration, scanning electron microscopy, gross dissection, and light microscopic examination of serial sections. The results show that the lower jaw carries some 60-65 functional teeth. In addition, numerous replacement teeth and tooth germs in various stages of development are located in a cavity in the dentary bone. Numerous nerve bundles are present in immediate relation to the dental follicles of tooth germs. Unerupted teeth do not contain light-microscopically discernible pulpal axons, but the pulps of functional teeth contain myelinated axons. Both perifollicular and pulpal nerve bundles derive from a nerve plexus, which is formed by branches from r. mandibularis trigemini. This nerve is easily accessible to experimental manipulation, where it courses through the adductor mandibulae muscular complex. Thus, the lower jaw of T. mariae seems to represent a suitable system for the study of tooth-nerve interactions in a polyphyodont species.

First molar tooth germs from 1-day-old mice were implanted into I mm holes prepared in the parietal bones of adult mice and left for 11, 14, 18 and 24 days. Seventy-four of 94 implanted tooth germs continued development with the formation of roots, periodontal ligament and new bone. This new bone fused with the old parietal bone thus establishing a true gomphosis between tooth and parietal bone.

The effects of methionine intubation via gastric needle on the growth of incisor and molar tooth germs in newborn rats were investigated. Upon delivery, the pups were divided into groups of 8 and randomly assigned to dams which were then randomly assigned to three groups. Then the pups were intubated in the stomach with (a) no methionine - group I, (b) 0.1 g methionine per 100 g body weight - group II, or (c) 0.2 g methionine - group III, from day 3 to day 13 on every other day. At day 15, the average body weights of pups among the three groups showed no difference statistically, though animals in group III showed a 17.5% mortality rate; there were no deaths in the other two groups. There was inadequate hair growth in some pups in group III. The weights of incisor and of molar tooth germs in group II were heavier than in groups I and III. The total hydroxyproline content of incisor tooth germs in group II was also greater than in the other groups, whereas there was no difference in molar tooth germs on this parameter among all groups. Collagen synthesis of both tooth germs was highest in group III compared to other groups. The total amount of calcium in both tooth germs showed no difference among groups, but values were consistently higher in group II. 45Ca uptake showed no difference among groups. The present results indicate that the amount of methionine received by growing pups alters the composition of developing tooth germs, but that incisor and molar tooth germs are affected differently.

Two dental morphological features, lower incisor shape and Carabelli trait on upper molars, were studied in Down's syndrome (DS) individuals and control groups. Lower incisors were smaller in DS in absolute terms, but showed a relatively greater mesiodistal crown dimension than labiolingual, the opposite relationship to normal. Although the Carabelli trait was present in a high percentage of DS subjects, few showed the cuspal form. These findings are consistent with the concept of a reduction of cellular activity of tooth germs reflecting a general retardation in growth in DS. The altered shape of the lower incisors may influence the pattern of periodontal disease observed in DS subjects.

This study explores whether the "distance gradient" model shown for embryonic development and postnatal tooth growth is also characteristic of the fetal period. Histologic data and ratings from 26 human fetuses show that, unlike the embryonic and postnatal periods, changes occurring in two tooth germs are significantly alike, regardless of the number of intervening teeth.

Fourteen rat dams with 8 pups each were fed either a 6, 12 or 20 per cent protein diet upon birth. Another group of 12 dams with the same number of pups was pair-fed either a 6, 12 or 20 per cent protein diet supplemented with caffeine (2 mg/100 g body weight). At day 15, randomly-selected pups were injected with [14C]-proline to determine collagen synthesis of the incisor and molar tooth germs. Another group of pups was used to determine calcium content of these tooth germs. Body weight, incisor weight and total calcium contents of tooth germs of pups from dams fed with 6 per cent protein diet were greater in the caffeine-supplemented group, whereas in the 20 per cent protein diet with caffeine group, these parameters were lower. The molar weights of the 12 per cent protein diet with caffeine animals were greater than the 12 per cent group without caffeine. The total hydroxyproline content of the incisor tooth germs from animals in the 12 per cent protein diet with caffeine was greater than is the non-caffeine group. However, total hydroxyproline of the molar tooth germs in the 20 per cent protein groups with caffeine was less than in the non-caffeine group. The rate of collagen synthesis of the incisor and molar tooth germs showed no difference in the presence or absence of caffeine in the 6, 12 and 20 per cent protein groups. Incisor and molar tooth germs are thus affected differently by the interaction of protein and caffeine, possibly due to differences in the pattern of tooth development.

The development of premolar tooth germs in dogs, particularly their rotation and crowding, was examined on radiographs, dissected specimens of tooth germs, serial sections stained by Masson-Goldner’s technique and reconstructed models. The materials used were the mandibles of 32 puppies from birth to 6 months, and the species was a highly pedigreed Shiba Inu which has no crowding of the premolars in the mature stage. The results obtained are as follows. (1) Rotations and crowdings of premolars, similar to those in brachygnathus dogs and wolves raised in captivity, were observed during ontogenesis of dolichocephalic dogs, whose adult state exhibits no crowding of teeth. (2) The type of rotation was B (the mesial portion is rotated buccally) for the second and third premolars and L (the mesial portion lingually) for the fourth premolar. (3) The rotations of the premolars did not coincide with those of their deciduous predecessors. (4) These rotations appeared in the bud and cap stages of premolars, before the formation of roots of deciduous molars. The premolars developed crowding at 5 months when they increased in dimension.

Mutant mice carrying the sex-linked gene Tabby (Ta), and others carrying crinkled (cr), an autosomal mimic of Ta, were studied histochemically with respect to the sulfhydryl: disulfide ratios in their skin and hair and the SH levels in their tooth germs. As compared to normal controls, the mutant animals demonstrated significantly elevated SH:S-S ratios (skin and hair) and SH levels (tooth germs) in the ectodermal components of these tissues. This finding corresponds with previously reported biochemical data on a form of human ectodermal dysplasia (ED), and therefore supports the hypothesis that these mutations in mice may be homologous to the genes for human ED.

– Odonotogenesis of the 2nd premoiar begins in the majority of cases at the age of 3–31/2 years, although this period can vary more widely than that for other permanent teeth. For this reason, aplasia of this, group of teeth cannot be diagnosed as early and with the same degree of certainty. A group of 104 children aged 3–7 years in whom one or more tooth germs mesial to the 1st permanent molar were not visible in the various age groups was reexamined radiographically in the region where they apparently lacked the development of tooth germs. The second examination tools place 16–24 months after the first, and a comparison was made of the two examinations. The study confirms that the 2nd premoiar can be very late in developing and that the chance of this being so is greater in the maxilla than in the mandible.

Functionally stable internal fixation is contraindicated for fractures of the pediatric mandible. The fracture affects two substrates that are extremely sensitive to outside influences: the bone tissue and the tooth germs. Irreversible growth disturbances can result from damage to these structures.

By using a slow rate of cooling, successful storage of developing teeth has been performed in liquid nitrogen. Dye exclusion tests indicate that 78 ± 8% of cells remain viable and transplantation to isologous hosts demonstrates that 86% of the stored developing teeth commence to grow and produce normal dental hard and soft tissue elements. The length of storage at −196 °C, for periods up to 3 months, appears to have no detrimental effect upon subsequent survival and development of tooth germs.

Upper and lower jaws of large and small specimens of the cod Gadus callarias were stained in toto by Alizarin and cleared in plastic to chart the distribution of ankylosed teeth and mineralized tooth germs. Other jaws of the same species were decalcified and transversely sectioned in series to reconstruct the dentition graphically. It was found that the dentition in Gadidae consists of several irregular longitudinal rows of functional, ankylosed teeth in each jaw. In the upper jaw the largest teeth were labially positioned, while in the lower jaw they were lingually positioned. A great number of teeth in all developmental stages were found in all positions within this area; within any of the rows of ankylosed teeth as well as between and outside these rows. Thus it was concluded that neither regular Zahnreihen nor tooth families existed in Gadidae and that in many teleosts the tooth replacement mechanism cannot be explained as a variant of the replacement mechanism in reptiles or other vertebrates where new teeth are added lingually or deep to the functional tooth row in a regular manner.

Publisher Summary The large size of the osteoclast, its multinuclearity, and the striated border in contact with absorbing bone form a striking histological picture that suggests that the cells are highly active and expend energy on a large scale. However, even up to the present time, comparatively little is known about their source, function, life span, or ultimate fate, although it is now over a century since their histological features were first described and illustrated. Inquiry into the biology of the osteoclast has passed through two main epochs and has at present entered a third. The typical osteoclast is a large, multinucleated cell, characteristically found on or near bone in process of absorption. This can be physiological, as for instance in the normal modelling of bone, or it can be the result of some pathological cause. The bone around the tooth germs in the embryonic jaw provides an excellent example of physiological absorption.