Over the past 50 years and more, many models have been proposed to explain how the nervous system is initially induced and how it becomes subdivided into gross regions such as forebrain, midbrain, hindbrain and spinal cord. Among these models is the 2-signal model of Nieuwkoop & Nigtevecht (1954), who suggested that an initial signal (‘activation’) from the organiser both neuralises and specifies the forebrain, while later signals (‘transformation’) from the same region progressively caudalise portions of this initial territory. An opposing idea emerged from the work of Otto Mangold (1933) and other members of the Spemann laboratory: 2 or more distinct organisers, emitting different signals, were proposed to be responsible for inducing the head, trunk and tail regions. Since then, evidence has accumulated that supports one or the other model, but it has been very difficult to distinguish between them. Recently, a considerable body of work from mouse embryos has been interpreted as favouring the latter model, and as suggesting that a ‘head organiser’, required for the induction of the forebrain, is spatially separate from the classic organiser (Hensen's node). An extraembryonic tissue, the ‘anterior visceral endoderm’ (AVE), was proposed to be the source of forebrain-inducing signals. It is difficult to find tissues that are directly equivalent embryologically or functionally to the AVE in other vertebrates, which led some (e.g. Kessel, 1998) to propose that mammals have evolved a new way of patterning the head. We will present evidence from the chick embryo showing that the hypoblast is embryologically and functionally equivalent to the mouse AVE. Like the latter, the hypoblast also plays a role in head development. However, it does not act like a true organiser. It induces pre-neural and pre-forebrain markers, but only transiently. Further development of neural and forebrain phenotypes requires additional signals not provided by the hypoblast. In addition, the hypoblast plays a role in directing cell movements in the adjacent epiblast. These movements distance the future forebrain territory from the developing organiser (Hensen's node), and we suggest that this is a mechanism to protect the forebrain from caudalising signals from the node. These mechanisms are consistent with all the findings obtained from the mouse to date. We conclude that the mechanisms responsible for setting up the forebrain and more caudal regions of the nervous system are probably similar among different classes of higher vertebrates. Moreover, while reconciling the two main models, our findings provide stronger support for Nieuwkoop's ideas than for the concept of multiple organisers, each inducing a distinct region of the CNS.

The three-dimensional (3D) microanatomy of the cornea is the major determinant of its optical and mechanical properties. Scanning electron microscopy (SEM) is the most commonly used method to obtain information on the overall 3D microanatomy of organs. However, SEM has not been successful in revealing the 3D microanatomy of the cornea, because the interior of the cornea is too compact to be explored by the electron beam. In this study, the 3D organisation of the cells and extracellular materials of human and rabbit corneas was examined after exposure by HCl and NaOH digestion, and by microdissection by the adhesive tape method. In the cornea of both species, all epithelial cells exhibited microplicae regardless of their location. This raises doubts about the tear film-holding role assigned to the microplicae of the superficial cells. Human and rabbit corneas differed in the collagen fibre patterns of the epithelial basement membranes. The 3D organisation of the stromal lamellae was similar in both species. In humans and rabbits, the keratocytes showed similar 3D features. However, the surface of human keratocytes located near Descemet's membrane exhibited small fenestrations that were not present in the rabbit keratocytes. The pattern of keratocyte innervation by the stromal neural plexus and 3D keratocyte microanatomy confirms that keratocytes form a large intercommunicating network within the corneal stroma. Two morphologically discrete subpopulations of keratocytes located at different stromal levels were identified in both human and rabbit corneas, suggesting that keratocytes are not functionally homogeneous. In addition, the density of the stromal neural plexus appeared to be greater in rabbits than in humans. Clear differences between human and rabbit corneas were observed in the collagen arrangement in Descemet's membrane, which may reflect their different biomechanical requirements.

An understanding of the origin of the sympathetic innervation of the upper limb is important in surgical sympathectomy procedures. An inconstant intrathoracic ramus which joined the 2nd intercostal nerve to the ventral ramus of the 1st thoracic nerve, proximal to the point where the latter gave a large branch to the brachial plexus, has become known as the ‘nerve of Kuntz’ (Kuntz, 1927). Subsequently a variety of sympathetic interneuronal connections down to the 5th intercostal space were reported and also described as the nerve of Kuntz. The aim of this study was to determine: (1) the incidence, location and course of the nerve of Kuntz; (2) the relationship of the nerve of Kuntz to the 2nd thoracic ganglion; (3) the variations of the nerve of Kuntz in the absence of a stellate ganglion; (4) to compare the original intrathoracic ramus with sympathetic variations at other intercostal levels; and (5) to devise an appropriate anatomical classification of the nerves of Kuntz.

Bilateral microdissection of the sympathetic chain and somatic nerves of the upper 5 intercostal spaces was undertaken in 32 fetuses (gestational age, 18 wk to full term) and 18 adult cadavers. The total sample size comprised 99 sides.

Sympathetic contributions to the first thoracic nerve were found in 60 of 99 sides (left 32, right 28). Of these, 46 were confined to the 1st intercostal space only. The nerve of Kuntz (the original intrathoracic ramus) of the 1st intercostal space had a demonstrable sympathetic connection in 34 cases, and an absence of macroscopic sympathetic connections in 12. In the remaining intercostal spaces, intrathoracic rami uniting intercostal nerves were not observed. Additional sympathetic contributions (exclusive of rami communicantes) were noted between ganglia, interganglionic segments and intercostal nerves as additional rami communicantes. The eponym nerve of Kuntz should be restricted to descriptions of the intrathoracic ramus of the 1st intercostal space. Any of these variant sympathetic pathways may be responsible for the recurrence of symptoms after sympathectomy surgery.

Programmed cell death or apoptosis occurred in anuran amphibian larval pancreas as a remodelling agent, and was responsible for the reduction of the gland volume during metamorphosis. Apoptotic cells were recognisable by their morphological characteristics and could be immunocytochemically detected by means of the TUNEL reaction, which evidenced nuclear DNA fragmentation. During the last stages of prometamorphosis, that is in the period of hindlimb differentiation, only a few TUNEL positive cells occurred, whereas they increased at the beginning of metamorphic climax, that is at forelimb emergence and during tail regression. Under the electron microscope, the typical morphological characteristics of apoptosis were observed: decrease in size, and the presence of wide intercellular spaces and nuclei with dense chromatin masses arranged in crescents. The fragmentation of these cells produced the so-called ‘apoptotic bodies’: portions of cytoplasm lined by a membrane, containing nuclear fragments and cytoplasmic organites. Dead cell elimination is hypothesised to occur by phagocytic ingestion.

The large literature on the human vomeronasal organ (VNO) offers little consensus as to its persistence in the adult. We have already documented the existence of the VNO from embryonic day 33 through the neonatal stages. This has now been extended to human adults: 27 cadaver nasal septa, aged 2–86 y, were either dissected or decalcified, serially sectioned, stained and examined. The consistent presence of the VNO is reported as a homologue, in the form of a duct-like structure on the nasal septum at all ages. Also reported are size variability, pronounced bilateral asymmetry, a nonchemosensory pseudostratified ciliated epithelium with considerable structural variation and generally without medial–lateral differentiation, nasal septal glands opening into the VNO lumen, a lack of correlation between postnatal age and VNO size, visualisation of the human VNO with certainty by histological means alone, and a minute opening as its only visible surface feature. The human VNO is a discrete structure that should not be confused with the nasopalatine fossa, the septal mucosal pits or VNO openings.

Previous mouse models have indicated that Otx1 and Otx2 play an important role in brain and sense organ development and, together with the Drosophila orthodenticle (otd) gene, they share a high degree of reciprocal functional equivalence. Interestingly, mouse models replacing the same region of the Otx2 locus with Otx1, otd or lacZ genes have revealed the existence of a differential post-transcriptional control between the visceral endoderm (VE) and epiblast cells. Indeed Otx1, otd or lacZ mRNA were transcribed in both tissues but translated only in the VE. Embryos lacking OTX1 or OTD proteins in the epiblast and derived tissues, such as the neuroectoderm and axial mesendoderm (AME), fail to maintain the anterior identity and result in a headless phenotype. This finding leads us to hypothesise that, during evolution, the specification of the vertebrate-type brain may have required epiblast cells to translate Otx2 mRNA in order to establish maintenance properties. The establishment of this regulatory control might have been reflected into a remarkable reorganisation of the rostral CNS architecture and might have represented an important event in the evolution of the vertebrate head. Current data suggest that the Otx2 replaced region and in particular the 3′ untranslated region (UTR), may contain regulatory element(s) necessary to translate and/or stabilise Otx2 mRNA in epiblast and its derivatives.

The steroidogenic interrenal cells in the adrenal homologue of the male stickleback (Gasterosteus aculeatus) were studied in relation to the reproductive cycle by means of histological and ultrastructural observations, and using histochemical methods for the localisation of 3β-hydroxysteroid dehydrogenase (3βHSD) and 17β-hydroxysteroid dehydrogenase (17βHSD). To determine the various stages of the reproductive cycle, the testes were also examined by histological and histochemical methods (3βHSD). The results indicate that in this teleost the interrenal cells can undergo a cycle in which phases characterised by different cytological aspects are observed. During this cycle there is a renewal of organelles, in particular mitochondria and SER. Periodic degenerative processes are also found. Organelle cytology showed that the cell cycle has at least 3 different aspects during the year. An analogy with some cytological aspects of the adrenal zonation in mammals is possible. It is postulated that the interrenal gland activity could substitute or supplement androgen production by the testes.

The purpose of this study was to document and compare the architectural parameters (fibre bundle length, angle of pennation) of human skeletal muscle in cadaveric specimens and live subjects. The medial (MG) and lateral (LG) gastrocnemius, and posterior (PS) and anterior (AS) soleus were examined bilaterally in 5 cadavers (mean age 72.6, range 65–83 y) and 9 live subjects (mean age 76.3, range 70–92 y). Data were obtained from direct measurement of cadaveric specimens and from ultrasonographic scans of the live subjects. In cadaveric muscle, fibre bundles were isolated; their length was measured in millimetres and pennation angles were recorded in degrees. In live muscle, similar measurements were taken from ultrasonographic scans of relaxed and contracted muscle. For the scans of relaxed muscle, subjects were positioned prone with the foot at a 90° angle to the leg, and for scans of contracted muscle, subjects were asked to sustain full plantarflexion during the scanning process. Fibre bundle length and angle of pennation were compared at matched locations in both groups. It was found that the relationship between cadaveric and in vivo values for fibre length and angle of pennation varied between muscle parts. The cadaveric architectural parameters did not tend to lie consistently towards either extreme of relaxation or contraction. Rather, within MG, PS and AS, cadaveric fibre bundle lengths lay between those for relaxed and contracted in vivo muscle. Similarly both the anterior and posterior cadaveric fibre angles of pennation lay between the in vivo values within LG and PS. In summary, architectural characteristics of cadaveric muscle differ from both relaxed and contracted in vivo muscle. Therefore, when developing models of skeletal muscle based on cadaveric studies, the architectural differences between live and cadaveric tissue should be taken into consideration.

The collagen fibrillar architectures in the general matrix of cartilage slices removed from both normal and osteoarthritic femoral heads were examined by both differential interference light microscopy and scanning electron microscopy. Whereas the normal general matrix contained a finely differentiated pseudo-random weave of fibrils developed from an interconnected array of radial elements, the osteoarthritic general matrix was characterised by the presence of structurally distinct regions consisting of strongly aligned radial bundles of fibrils and associated intense tangles or ‘knotted’ features. Simple structural models were developed to explore possible transformation structures based on two different types of interconnectivity in the three-dimensional fibrillar network. These models support the hypothesis that the distinctive ultrastructural features of the osteoarthritic general matrix can develop as a consequence of largely passive degradative changes occurring in the fibrillar weave originally present in the normal matrix. This could, in principle, occur independently of any new structure that might develop as a consequence of any upregulation of collagen associated with the osteoarthritic process.

This study investigated the relationships between the density of Meissner's corpuscles and the dermatoglyphic characteristics of human fingers. Dermatoglyphic prints and tissue samples were collected from the index (II) and ring (IV) fingers of 28 cadavers from the Medical School, University of Adelaide. Pattern types, pattern intensity, total ridge count and ridge breadth, were determined for each sample and the density of Meissner's corpuscles established by recording the mean number of Meissner's corpuscles underlying a 10 mm long line on the skin surface. No relationship was found between the density of Meissner's corpuscles and pattern type, pattern intensity or total ridge count. Negative correlations were found for the density of Meissner's corpuscles with both ridge width and size of fingers. Males were found to have significantly larger fingers, larger ridge breadth, and a lower density of Meissner's corpuscles per 10 mm compared with females. However, there was no difference between the total number of Meissner's corpuscles per finger in males and females. No significant differences were found in either the density of Meissner's corpuscles between antimeres or between the index and ring fingers. These results suggest that for both the left and right hand in males and females, there is a similar number of Meissner's corpuscles for both the index and ring fingers.

The aim of the present study was to locate the sensory and autonomic ganglia innervating the female genital musculature in pigs. The retrograde neuronal tracers horseradish peroxidase (HRP) or fast blue (FB) were injected into the left retractor clitoridis muscle (RCM), which was treated as a typical model of the genital smooth musculature. Labelled cells were found in ipsilateral dorsal root ganglia Sl–S4, in bilateral sympathetic paravertebral ganglia from L5–L6 or L6–L7 to S3 and in the left and right caudal mesenteric ganglion. In two of the five animals treated, presumably preganglionic parasympathetic cells were labelled in the ipsilateral intermediate grey substance of the segments Sl–S2.

This study was undertaken to investigate the morphological characteristics and lectin affinity of the testicular lamina propria in healthy boars and in unilateral and bilateral abdominal cryptorchid boars. The lamina propria of scrotal testes from healthy boars and unilateral cryptorchid boars was constituted by an innermost noncellular layer, the basal lamina, and by 2 layers of peritubular cells, each separated by a fibrous layer. The noncellular layers contained collagen fibres and glycoconjugates with abundant N-acetylgalactosamine, galactose, fucose, N-acetylglucosamine and neuraminic acid residues. The inner peritubular cell layer was composed of myoid cells, the outer layer of fibroblasts. In the abdominal testes of unilateral and bilateral cryptorchid boars, the lamina propria of nondegenerating and degenerating seminiferous tubules appeared thickened due to an increased content of collagen fibres and glycoconjugates. Glycoconjugates showed decreased amounts of fucose, neuraminic acid and galactose, and increased amounts of N-acetylglucosamine residues. The basal lamina formed infoldings toward the seminiferous epithelium and contained small cells. Both inner and outer peritubular cells were fibroblasts of immature appearance. In degenerated seminiferous tubules of bilateral cryptorchid boars, the lamina propria was composed of a thickened and collagenised basal lamina, without peritubular cells and with a low content of glycoconjugates. In scrotal testes, therefore, the lamina propria was implicated in tubular contractility and in mediating the communication and the substrate diffusion between seminiferous tubules and interstitial tissue. Cryptorchidism induced morphological and histochemical alterations in the lamina propria of abdominal testes, which may be linked to evidence from other studies of lack of tubular contractility and defective cell–cell communication and substrate diffusion. The severity of these anomalies correlated with the severity of Sertoli cell alterations.

The ultrastructure of Betz cells in the 5th layer of the primary motor cortex of 17 neurologically and psychiatrically normal control individuals was studied. Normal-appearing Betz cells showed a wide range of features including novel electron-dense inclusion bodies (Bunina-like bodies) resembling Bunina bodies characteristic of amyotrophic lateral sclerosis (ALS), accumulations of neurofilaments (10 nm in diameter), bundles of filaments (20–25 nm in diameter) thicker than neurofilaments, lamellar structures, lamellar bodies and structures similar to Hirano bodies. Among these ‘abnormal’ features, the presence of Bunina-like bodies may be an age-related nonspecific degenerative change, since they appeared more frequently in elderly individuals. The presence of these abnormal features—particularly the Bunina-like bodies—in the Betz cells of normal human brains must be considered in the assessment of the pathognomonic significance of such structures in ALS and other neurological diseases that affect the motor cortex.

The epithalamus is a major subdivision of the diencephalon constituted by the habenular nuclei and pineal complex. Structural asymmetries in this region are widespread amongst vertebrates and involve differences in size, neuronal organisation, neurochemistry and connectivity. In species that possess a photoreceptive parapineal organ, this structure projects asymmetrically to the left habenula, and in teleosts it is also situated on the left side of the brain. Asymmetries in size between the left and right sides of the habenula are often associated with asymmetries in neuronal organisation, although these two types of asymmetry follow different evolutionary courses. While the former is more conspicuous in fishes (with the exception of teleosts), asymmetries in neuronal organisation are more robust in amphibia and reptiles. Connectivity of the parapineal organ with the left habenula is not always coupled with asymmetries in habenular size and/or neuronal organisation suggesting that, at least in some species, assignment of parapineal and habenular asymmetries may be independent events.

The evolutionary origins of epithalamic structures are uncertain but asymmetry in this region is likely to have existed at the origin of the vertebrate, perhaps even the chordate, lineage. In at least some extant vertebrate species, epithalamic asymmetries are established early in development, suggesting a genetic regulation of asymmetry. In some cases, epigenetic factors such as hormones also influence the development of sexually dimorphic habenular asymmetries. Although the genetic and developmental mechanisms by which neuroanatomical asymmetries are established remain obscure, some clues regarding the mechanisms underlying laterality decisions have recently come from studies in zebrafish. The Nodal signalling pathway regulates laterality by biasing an otherwise stochastic laterality decision to the left side of the epithalamus. This genetic mechanism ensures a consistency of epithalamic laterality within the population. Between species, the laterality of asymmetry is variable and a clear evolutionary picture is missing. We propose that epithalamic structural asymmetries per se and not the laterality of these asymmetries are important for the behaviour of individuals within a species. A consistency of the laterality within a population may play a role in social behaviours between individuals of the species.

Splanchnic neurectomy is of value in the management of chronic abdominal pain. It is postulated that the inconsistent results of splanchnicectomies may be due to anatomical variations in the pattern of splanchnic nerves. The advent of minimally invasive and video-assisted surgery has rekindled interest in the frequency of variations of the splanchnic nerves. The aims of this study were to investigate the incidence, origin and pattern of the splanchnic nerves in order to establish a predictable pattern of splanchnic neural anatomy that may be of surgical relevance. Six adult and 14 fetal cadavers were dissected (n = 38). The origin of the splanchnic nerve was bilaterally asymmetrical in all cases. The greater splanchnic nerve (GSN) was always present, whereas the lesser splanchnic nerve (LSN) and least splanchnic nerve (lSN) were inconsistent (LSN, 35 of 38 sides (92%); LSN, 21 of 38 sides (55%). The splanchnic nerves were observed most frequently over the following ranges: GSN, T6–9: 28 of 38 sides (73%); LSN, when present, T10–11: (10 of 35 sides (29%); and lSN, T11–12: 3 of 21 sides (14%). The number of ganglionic roots of the GSN varied between 3 and 10 (widest T4–11; narrowest, T5–7). Intermediate splanchnic ganglia, when present, were observed only on the GSN main trunk with an incidence of 6 of 10 sides (60%) in the adult and 11 of 28 sides (39%) in the fetus. The higher incidence of the origin of GSN above T5 has clinical implications, given the widely discussed technique of undertaking splanchnicectomy from the T5 ganglion distally. This approach overlooks important nerve contributions and thereby may compromise clinical outcome. In the light of these variations, a reappraisal of current surgical techniques used in thoracoscopic splanchnicectomy is warranted.

Recent studies of protochordates (ascidian tunicates and amphioxus) have given insights into possible ancestors of 2 of the characteristic features of the vertebrate head: neural crest and placodes. The neural crest probably evolved from cells on either side of the neural plate–epidermis boundary in a protochordate ancestral to the vertebrates. In amphioxus, homologues of several vertebrate neural crest marker genes (BMP2/4, Pax3/7, Msx, Dll and Snail) are expressed at the edges of the neural plate and/or adjacent nonneural ectoderm. Some of these markers are also similarly expressed in tunicates. In protochordates, however, these cells, unlike vertebrate neural crest, neither migrate as individuals through embryonic tissues nor differentiate into a wide spectrum of cell types. Therefore, while the protochordate ancestor of the vertebrates probably had the beginnings of a genetic programme for neural crest formation, this programme was augmented in the earliest vertebrates to attain definitive neural crest. Clear homologues of vertebrate placodes are lacking in protochordates. However, both amphioxus and tunicates have ectodermal sensory cells. In tunicates these are all primary neurons, sending axons to the central nervous system, while in amphioxus, the ectodermal sensory cells include both primary neurons and secondary neurons lacking axons. Comparisons of developmental gene expression suggest that the anterior ectoderm in amphioxus may be homologous to the vertebrate olfactory placode, the only vertebrate placode with primary, not secondary, neurons. Similarly, biochemical, morphological and gene expression data suggest that amphioxus and tunicates also have homologues of the adenohypophysis, one of the few vertebrate structures derived from nonneurogenic placodes. In contrast, the origin of the other vertebrate placodes is very uncertain.

The tilting angle and the shape of the glenoid cavity are considered to relate closely to shoulder stability. They are also important when planning arthroplasty and developing new designs. This study examines the glenoid cavity using 3-dimensional MRI. Forty volunteers (20 men, 20 women; average age 21.4; range 18–35 y) were enrolled in the study. The tilting angles of the glenoid bone were measured in 5 consecutive axial planes perpendicular to the glenoidal long axis. Cross sections were divided into 3 types (concave, flat, convex) according to the shape on each plane.

The average tilting angles for the 5 planes from the bottom to the top were 3.3±4.1, 1.4±3.8, −0.6±1.9, −1.4±3.3, and −6.2±3.3 degrees anteriorly, indicating that the 3-dimensional bony structure of the glenoid was twisted anteriorly to posteriorly. Images on the bottom plane consisted of 82.5% concave type, 15% flat type and 2.5% convex type, while only 3 cases (7.5%) showed concave at the top plane. The shape of the glenoid cavity is thought to be conducive to glenohumeral motion and stability.

Aponeurotic deformation measurements have traditionally been taken by loading dissected muscles; thus the values obtained may not reflect in vivo function. In the present study, we estimated dimensional changes in the central aponeurosis of the intact human tibialis anterior muscle upon loading induced by muscle contraction. Measurements were taken in seven males, and involved real-time ultrasound scanning of the tibialis anterior muscle at 30° of plantarflexion at rest and during isometric dorsiflexion maximum voluntary contraction (MVC). At each contraction state, the length of the aponeurosis, the width along its length, and its area were estimated from sagittal-plane and axial-plane sonographs. In the transition from rest to MVC, the length of the aponeurosis increased by 7% (P < 0.05), its width increased by up to 21% (P < 0.05), and its area increased by 17% (P < 0.05). These results indicate that the in vivo tibialis anterior aponeurosis behaves as a compliant material upon active muscle shortening. The methodology employed allows cross-sectional and longitudinal design investigations, circumventing the problems associated with epimysial removal under in vitro experimental conditions.

References to histochemistry are extensive for human limb muscles but occur less frequently in relation to vertebral muscle. Most vertebral muscle literature has been concerned with muscle fibre characteristics in the lumbar and thoracic spine, due in large part to the incidence of low back pain and idiopathic scoliosis. However few studies have investigated the histochemical composition of neck muscles in humans: and, to our knowledge, no previous study has examined the antagonistic longus colli and multifidus muscle pair. In addition, while age-related segmental degeneration is most prominent between C5 and C7, it is not known whether these osteoligamentous changes are paralleled by changes in muscle fibre ratio. Tissue blocks comprising muscle and bone from C5–C7 segments were harvested at autopsy from 16 subjects with ages ranging from 4 to 77 years. The prevertebral longus colli and postvertebral multifidus muscle pairs were randomly selected from one or other side in each subject. The tissue was frozen, sectioned and histochemically stained for myofibrillar adenosine triphosphatase. Analysis of muscle fibre types was performed by light microscopy. Wilcoxon paired t-tests were used to ascertain whether intramuscular and intermuscular differences in fibre composition were significant. In addition, correlation and regression analyses were used to determine whether fibre type proportions changed in either muscle with increasing age. The present study has revealed histochemical differences between longus colli and multifidus at the level of the C5–C7 vertebral segments. Multifidus comprises a significantly greater proportion of type I than type II fibres. Longus colli comprises a significantly greater proportion of type II fibres than multifidus. Further there were no changes in fibre type proportion in either muscle with increasing age. These observations suggest that longus colli responds equally to postural and phasic demands, whereas multifidus is predominantly postural. Also it would appear that age-related structural alterations in lower cervical segments are not paralleled by changes in muscle fibre ratio.

Blind mole-rats (Spalax ehrenbergi) are fossorial solitary rodents that present striking morphological, physiological and behavioural adaptations to the subterranean environment in which they live. Previous studies have shown that mole-rats are specialised in tooth-digging. The rapid eruption-rate of their incisors has evolved to compensate for their excessive wear by excavation. Males use their incisors more than females for digging and fighting, and their rate of incisor eruption is significantly more rapid than in females. Since mole-rats use their incisors for digging throughout the year, we suggest that continuous mechanical pressure on their oral tissues concentrated at the apical sites of the upper incisors leads to cell and tissue fatigue. We provide evidence for 5 stages of palatal perforation by the upper incisors at their apical sites, with maximum perforation characterising aged males. Interspecies comparisons with 7 other fossorial and semi-fossorial rodent species, and with beavers, which expose their incisors to enormous mechanical pressure, revealed that this palatal perforation is unique to the male mole-rat. We suggest that while the fast eruption rate of incisors in the mole-rat compensates for the rapid wear resulting from digging, evolutionary adaptation to continuous tooth-digging is still ongoing, since the physical pressure of digging at the apical sites of the upper incisors leads to tissue destruction, breakage of the palatal bone and possibly to death, as a result of maxillary inflammation.