Faculty Bibliography

Characterizing dental development in fossil hominins is important for distinguishing between them and for establishing where and when the slow overall growth and development of modern humans appeared. Dental development of australopiths and early Homo was faster than modern humans. The Atapuerca fossils (Spain) fill a barely known gap in human evolution, spanning ~1.2 to ~0.4 million years (Ma), during which H. sapiens and Neandertal dental growth characteristics may have developed. We report here perikymata counts, perikymata distributions and periodicities of all teeth belonging to the TE9 level of Sima del Elefante, level TD6.2 of Gran Dolina (H. antecessor) and Sima de los Huesos. We found some components of dental growth in the Atapuerca fossils resembled more recent H. sapiens. Mosaic evolution of perikymata counts and distribution generate three distinct clusters: H. antecessor, Sima de los Huesos and H. sapiens.

Deeper or more 'severe' linear enamel hypoplasia (LEH) defects are hypothesized to reflect more severe stress during development, but it is not yet clear how depth is influenced by intrinsic enamel growth patterns. Recent work documented inter- and intraspecific differences in LEH defect depth in extant great apes, with mountain gorillas having shallower defects than other taxa, and females having deeper defects than males. Here, we assess the correspondence of inter- and intraspecific defect depth and intrinsic aspects of enamel growth: enamel extension rates, outer enamel striae of Retzius angles, and linear enamel thickness. Thin sections of great ape canines (n = 40) from Gorilla beringei beringei, Gorilla gorilla gorilla, Pan troglodytes, and Pongo spp. were analyzed. Enamel extension rates were calculated within deciles of enamel-dentine junction length. Linear enamel thickness and the angle of intersection between striae of Retzius and the outer enamel surface were measured in the imbricational enamel. Mountain gorillas have faster enamel extension rates and shallower striae angles than the other taxa examined. Mountain gorillas have thinner imbricational enamel than western lowland gorillas and orangutans, but not chimpanzees. In the combined-taxon sample, females exhibit larger striae angles and thicker imbricational enamel than males. Enamel extension rates are highly negatively correlated with striae angles and LEH defect depth. Enamel growth variation corresponds with documented inter- and intraspecific differences in LEH defect depth in great ape canines. Mountain gorillas have shallower striae angles and faster extension rates than other taxa, which might explain their shallow LEH defect morphology and the underestimation of their LEH prevalence in previous studies. These results suggest that stressors of similar magnitude and timing might produce defects of different depths in one species or sex vs. another, which has implications for interpretations of stress histories in hominins with variable enamel growth patterns.

An error slipped into Table 1 of this article. The data in the sixth column (OC Area) is incorrect. The correct table is given below. We apologize to our readers. Une erreur s'est glissée dans le Tableau 1 de l'article en référence. Les données de la sixième colonne (OC Area) sont incorrectes. Le tableau correct est donné ci-dessous. Nous prions nos lecteurs de bien vouloir excuser cette coquille.

Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and vascular endothelial growth factor. In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signalling, but also parenchymal dentin via the Wnt/β-catenin pathway. In an orthotopic large-animal model following parenchyma and stroma ablation, Wnt3a-recruited endogenous cells regenerated neurovascular stroma and differentiated into parenchymal odontoblast-like cells that extended the processes into newly formed dentin with a structure-mechanical equivalency to native dentin. Thus, the Alx3-Wnt3a axis enables postnatal progenitors with a modest innate regenerative capacity to regenerate adult tissues. Depleted signals in the decellularized matrix may be reinstated by a developmentally pivotal gene or corresponding protein.

The face is the most distinctive feature used to identify others. Modern humans have a short, retracted face beneath a large globular braincase that is distinctively different from that of our closest living relatives. The face is a skeletal complex formed by 14 individual bones that houses parts of the digestive, respiratory, visual and olfactory systems. A key to understanding the origin and evolution of the human face is analysis of the faces of extinct taxa in the hominin clade over the last 6 million years. Yet, as new fossils are recovered and the number of hominin species grows, the question of how and when the modern human face originated remains unclear. By examining key features of the facial skeleton, here we evaluate the evolutionary history of the modern human face in the context of its development, morphology and function, and suggest that its appearance is the result of a combination of biomechanical, physiological and social influences.

Store-operated Ca²⁺ entry (SOCE) channels are highly selective Ca²⁺ channels activated by the endoplasmic reticulum (ER) sensors STIM1 and STIM2. Their direct interaction with the pore-forming plasma membrane ORAI proteins (ORAI1, ORAI2, and ORAI3) leads to sustained Ca²⁺ fluxes that are critical for many cellular functions. Mutations in the human ORAI1 gene result in immunodeficiency, anhidrotic ectodermal dysplasia, and enamel defects. In our investigation of the role of ORAI proteins in enamel, we identified enamel defects in a patient with an ORAI1 null mutation. Targeted deletion of the Orai1 gene in mice showed enamel defects and reduced SOCE in isolated enamel cells. However, Orai2^-/- mice showed normal enamel despite having increased SOCE in the enamel cells. Knockdown experiments in the enamel cell line LS8 suggested that ORAI2 and ORAI3 modulated ORAI1 function, with ORAI1 and ORAI2 being the main contributors to SOCE. ORAI1-deficient LS8 cells showed altered mitochondrial respiration with increased oxygen consumption rate and ATP, which was associated with altered redox status and enhanced ER Ca²⁺ uptake, likely due to S-glutathionylation of SERCA pumps. Our findings demonstrate an important role of ORAI1 in Ca²⁺ influx in enamel cells and establish a link between SOCE, mitochondrial function, and redox homeostasis.

Despite their importance for understanding the evolutionary foundations of modern human senescence, available data on aging processes in nonhuman primates from well-studied natural environments are rare, with notable exceptions. We examined patterns of skeletal aging in Virunga mountain gorillas from Volcanoes National Park, Rwanda. Virunga gorillas are distinctive in their herbivory, increased terrestriality, and accelerated life history compared to other great apes. Data were collected from naturally accumulated skeletons [N=50 M, 39 F, 5 Unk], including 53 known-age individuals (0-43 years). Virunga gorillas do not show the dental senescence reported in some other primates. While molar percent dentine exposure significantly increases with age, and occlusal topography metrics significantly decrease with age, 3D relative shearing crest length is maintained, even in heavily worn teeth. Periodontal disease, evidenced by alveolar bone loss, increases significantly with age in molars but not premolars. Degenerative bone changes are also common. Degenerative joint disease (eburnation, osteophytes, porosity) significantly increases with age for all joints (forelimb, hindlimb, vertebrae). However, the strength of correlations differs across body compartments and sexes. Long bone diaphyses show medullary expansion and cortical thinning with age, and periosteal expansion that preserves bone strength despite endosteal bone loss. Fore-tohindlimb strength decreases with age in Virunga gorilla females, possibly associated with behavioral changes, but they lack the rapid bone loss characteristic of post-menopausal human females. Skeletal aging processes in Virunga gorillas and other primates may be influenced by local ecology and behavior, and provide insights into the unique features of human aging

Bone tissue is an inorganic-organic composite made of hydroxyapatite mineral, collagen fibers, and cement (non-collagenous proteins). Although the mineral component hydroxyapatite is negatively birefringent and represents over 65% of bone weight, undecalcified bone sections imaged by polarization microscopy show a predominant positive birefringence. The analysis of bone mineral thus relies on other methods, such as electron microscopy or imaging methods based on X-rays that have shown the hydroxyapatite phase to consist of nanometric-sized platelets arranged parallel to the collagen fibers. In this study we attempt to visualize the mineral phase using polarization microscopy. Samples from human cortical bone were rendered anorganic by: i) heating the samples at 200degreeC for 24 hours, or ii) treating with (0.5%) NaOCl solution at 50degreeC for 3 days. Samples were then prepared for and observed by polarization microscopy, which demonstrated a birefringence specific for the mineral phase. To better characterize the mineral, we focused on osteonal lamellae of very thin sections (< 10mum-thick) using polarization microscopy configured with several compensators (1/4 -lambda, 3/4- lambda, 1- lambda, 1 1/4 lambda). The high spatial resolution images identified mineral grains of micrometric size (0.43 +/-0.07 mum diameter). As a result of small changes in the relative retardation of the O-and E-rays, these grains were optically stained, exhibiting different interference colors. These grains are interpreted as mineral-packets in which the crystals present the same orientation of their optic axis. They exhibited the original fibrous texture and were arranged in an orderly fashion relating to the lamellar microarchitecture

Linear enamel hypoplasia (LEH) appears as pronounced horizontal grooves on the outer surface of teeth. LEH defects are understood to represent episodes of nonspecific stress in early life, but little is known about their etiology in nonhuman primates. Researchers have suggested that more severe stressors result in deeper LEH defects, while others argue that depth is related to enamel geometry, i.e., larger or smaller striae angles, reflecting differences in growth rates. Here we ask whether inter- and intraspecific variation in enamel growth corresponds with documented differences in defect depth among great apes. Enamel extension rate (EER), or the rate at which teeth grow in height, was assessed using histological methods in canines of four taxa (Gorilla beringei, Gorilla gorilla, Pan troglodytes, Pongo sp., N=16). While sample sizes are too small for statistical comparisons, mountain gorillas have faster EER, and show no overlap with other taxa in the middle 3/5ths of crown height, where LEH defects most commonly occur. This matches our previously reported pattern of defect depth, with mountain gorillas having shallower defects than other taxa in the same crown region. In general, males have faster extension rates than females, but there is some overlap, particularly outside the midcrown. We found that EER is negatively correlated with defect depth (r2=0.66, p<0.001). These results suggest that enamel growth variation influences LEH defect morphology, with faster-growing crowns having shallower defects. However, stress severity may also play an important role in defect formation and help to explain the appearance of particularly deep defects