No / Paleoanthropological studies often center on teeth, not only because these elements are commonly preserved in the fossil record, but because they apparently contain a wealth of information with regard to development, phylogeny, and function. However, despite a plethora of studies, somefundamental problems are still unresolved. For example, while it is recognized that the 3-dimensional arrangement of enamel prisms may hold important information with regard to phylogeny (von Koenigswald and Sander, 1997) and function (Rensberger, 2000), many paleoanthropological studies have thus far relied on investigating enamel microanatomy as a 2-dimensional structure (e.g., Dean et al., 2001 C Dean, M.G Leakey, D Reid, F Schrenk, G.T Schwartz, C Stringer and A Walker, Growth processes in teeth distinguish modern humans from Homo erectus an earlier hominins, Nature 414 (2001), pp. 628¿631. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (120)Dean et al., 2001). This is mainly due to difficulties in visualizing and quantifying the 3-D structure of prisms. In order to overcome these limitations a computer model was developed (Jiang et al., 2003) which attempted to simulate the effects of biophysical processes governing enamel formation in modern humans (adapted from Osborn, 1970). Here we extend our model and present preliminary data on inter-specific variation in prism arrangement among primates. Furthermore, during our work torecreate the 3D microstructure of prismatic enamel it became increasingly clear that there are not only limitations with previous dental growth studies, but that these studies are based on fundamentally different concepts regarding evolutionary processes from those assumed in our approach. These limitations and differences will be highlighted also.

abstract: Despite the critical role that the vertebral column plays in postural and locomotor behaviors, the functional morphology of the cervical region (i.e., the bony neck) remains poorly understood, particularly in comparison to that of the thoracic and lumbar sections. This dissertation tests the hypothesis that morphological variation in cervical vertebrae reflects differences in positional behavior (i.e., suspensory vs. nonsuspensory and orthograde vs. pronograde locomotion and postures). Specifically, this project addresses two broad research questions: (1) how does the morphology of cervical vertebrae vary with positional behavior and cranial morphology among primates and (2) where does fossil hominoid morphology fall within the context of the extant primates. Three biomechanical models were developed for the primate cervical spine and their predictions were tested by conducting a comparative analysis using a taxonomically and behaviorally diverse sample of primates. The results of these analyses were used to evaluate fossil hominoid morphology. The two biomechanical models relating vertebral shape to positional behaviors are not supported. However, a number of features distinguish behavioral groups. For example, the angle of the transverse process in relation to the cranial surface of the vertebral body--a trait hypothesized to reflect the deep spinal muscles' ability to extend and stabilize the neck--tends to be greater in pronograde species; this difference is in the opposite of the direction predicted by the biomechanical models. Other traits distinguish behavioral groups (e.g., spinous process length and cross-sectional area), but only in certain parts of the cervical column. The correlation of several vertebral features, especially transverse process length and pedicle cross-sectional area, with anterior cranial length supports the predictions made by the third model that links cervical morphology with head stabilization (i.e., head balancing). Fossil hominoid cervical remains indicate that the morphological pattern that characterizes modern humans was not present in Homo erectus or earlier hominins. These hominins are generally similar to apes in having larger neural arch cross-sectional areas and longer spinous processes than modern humans, likely indicating the presence of comparatively large nuchal muscles. The functional significance of this morphology remains unclear. / Dissertation/Thesis / Ph.D. Anthropology 2013

Dans le cadre de ce mémoire, les relations entre morphologie, locomotion et croissance chez les hominoïdes sont analysées sous l'angle des proportions métaphysaires et de leur acquisition. Plusieurs niveaux d'analyse — intermembre, supérieur et inférieur — sont abordés dans une perspective ontogénique. La masse corporelle et la direction des charges influencent la morphologie des surfaces articulaires et métaphysaires mais aussi leur développement. Les charges étant dépendantes du mode locomoteur et celui-ci se modifiant en fonction de l'âge, on tente de voir à quel(s) moment(s) les changements proportionnels ont lieu et pourquoi ils apparaissent. Des mesures linéaires ont été recueillies sur l'humérus, le radius, le fémur et le tibia sur un échantillon squelettique des espèces H. sapiens, P. troglodytes, G. gorilla et P. pygmaeus. À partir de ces mesures et du calcul de certains ratios, des comparaisons intra et interspécifiques ont été réalisées. Les différences les plus significatives entre les espèces se dévoilent au niveau intermembre et sont relatives aux différents pourcentages d'utilisation des membres supérieurs ou inférieurs. Au sein des espèces, les résultats révèlent une similarité dans les réactions des surfaces métaphysaires au niveau intermembre, supérieur et inférieur. Les changements proportionnels ont lieu entre les stades 0 et 1 pour H. sapiens (première marché indépendante), entre les stades 2 et 4 pour P. troglodytes (majorité du poids corporel soutenue par les membres inférieurs) et entre les stades 3 et 5 pour G. gorilla (taille adulte et quadrupédie très majoritaire). Pour P. pygmaeus aucun stade en particulier n'a été ciblé par les analyses et cela concorde avec l'homogénéité de ses modes de locomotion employés au cours de la vie. Les différences proportionnelles répondent à des changements locomoteurs majeurs. Australopithecus afarensis est intermédiaire entre H. sapiens et les grands singes pour de nombreuses comparaisons. Au niveau du genou, les plus jeunes individus A. afarensis ne montrent pas de morphologie bipède, similaire aux humains. / This thesis analyses the relationship between morphology, locomotion and growth in hominoids by studying metaphyseal proportions and development. Several levels of analysis — interlimb, upper and lower limbs — are discussed in an ontogenic perspective. Body mass and direction of loads affect the morphology of articular and metaphyseal surfaces but also their development. Taking into account the locomotion of a species and related loads during growth, we try to determine when proportions change, if at all, and why they appear. Australopithecus afarensis is one species for which the debate about its locomotion is still ongoing, study of the ontogeny of its proportions may shed light on the functions of its limbs during locomotion. Linear measurements were collected on the humerus, radius, ulna, femur and tibia of H. sapiens, P. troglodytes, G. gorilla and P. pygmaeus. From these measurements, ratios have been calculated to intra and inter limb proportions of hominoid appendicular skeleton for different age groups. Differences between species are most significant at the interlimb level and relative to the different relative percentage of upper and lower limbs use. Within species, results reveal a similarity for metaphyseal surfaces responses to loads at all levels of analyses. Proportional changes take place between dental stages 0 and 1 for H. sapiens (acquisition of bipedality), between stages 2 and 4 for P. troglodytes (majority of body weight supported by the lower limb) and between stages 3 and 5 for G. gorilla (knuckle-walking for 85 % of the time). For P. pygmaeus, no proportional change occur at any specific stage, which corresponds to the absence of changes in locomotor behavior from birth to adulthood in that species. From these data, it appears that proportional differences are responses to major changes in the mode of locomotion. Australopithecus afarensis is intermediate between H. sapiens and apes for many proportional comparisons while the knee joint, contrarily to expectation, is not like the bipedal humans.

Dans le cadre de ce mémoire, les relations entre morphologie, locomotion et croissance chez les hominoïdes sont analysées sous l'angle des proportions métaphysaires et de leur acquisition. Plusieurs niveaux d'analyse — intermembre, supérieur et inférieur — sont abordés dans une perspective ontogénique. La masse corporelle et la direction des charges influencent la morphologie des surfaces articulaires et métaphysaires mais aussi leur développement. Les charges étant dépendantes du mode locomoteur et celui-ci se modifiant en fonction de l'âge, on tente de voir à quel(s) moment(s) les changements proportionnels ont lieu et pourquoi ils apparaissent. Des mesures linéaires ont été recueillies sur l'humérus, le radius, le fémur et le tibia sur un échantillon squelettique des espèces H. sapiens, P. troglodytes, G. gorilla et P. pygmaeus. À partir de ces mesures et du calcul de certains ratios, des comparaisons intra et interspécifiques ont été réalisées. Les différences les plus significatives entre les espèces se dévoilent au niveau intermembre et sont relatives aux différents pourcentages d'utilisation des membres supérieurs ou inférieurs. Au sein des espèces, les résultats révèlent une similarité dans les réactions des surfaces métaphysaires au niveau intermembre, supérieur et inférieur. Les changements proportionnels ont lieu entre les stades 0 et 1 pour H. sapiens (première marché indépendante), entre les stades 2 et 4 pour P. troglodytes (majorité du poids corporel soutenue par les membres inférieurs) et entre les stades 3 et 5 pour G. gorilla (taille adulte et quadrupédie très majoritaire). Pour P. pygmaeus aucun stade en particulier n'a été ciblé par les analyses et cela concorde avec l'homogénéité de ses modes de locomotion employés au cours de la vie. Les différences proportionnelles répondent à des changements locomoteurs majeurs. Australopithecus afarensis est intermédiaire entre H. sapiens et les grands singes pour de nombreuses comparaisons. Au niveau du genou, les plus jeunes individus A. afarensis ne montrent pas de morphologie bipède, similaire aux humains. / This thesis analyses the relationship between morphology, locomotion and growth in hominoids by studying metaphyseal proportions and development. Several levels of analysis — interlimb, upper and lower limbs — are discussed in an ontogenic perspective. Body mass and direction of loads affect the morphology of articular and metaphyseal surfaces but also their development. Taking into account the locomotion of a species and related loads during growth, we try to determine when proportions change, if at all, and why they appear. Australopithecus afarensis is one species for which the debate about its locomotion is still ongoing, study of the ontogeny of its proportions may shed light on the functions of its limbs during locomotion. Linear measurements were collected on the humerus, radius, ulna, femur and tibia of H. sapiens, P. troglodytes, G. gorilla and P. pygmaeus. From these measurements, ratios have been calculated to intra and inter limb proportions of hominoid appendicular skeleton for different age groups. Differences between species are most significant at the interlimb level and relative to the different relative percentage of upper and lower limbs use. Within species, results reveal a similarity for metaphyseal surfaces responses to loads at all levels of analyses. Proportional changes take place between dental stages 0 and 1 for H. sapiens (acquisition of bipedality), between stages 2 and 4 for P. troglodytes (majority of body weight supported by the lower limb) and between stages 3 and 5 for G. gorilla (knuckle-walking for 85 % of the time). For P. pygmaeus, no proportional change occur at any specific stage, which corresponds to the absence of changes in locomotor behavior from birth to adulthood in that species. From these data, it appears that proportional differences are responses to major changes in the mode of locomotion. Australopithecus afarensis is intermediate between H. sapiens and apes for many proportional comparisons while the knee joint, contrarily to expectation, is not like the bipedal humans.

En aquest treball es presenta l'evolució molecular i estudi funcional de gens localitzats a les duplicacions segmentàries de la regió 7q11.23, implicada en la Síndrome de Williams-Beuren (SWB). S'ha datat l'aparició d'aquestes duplicacions en els últims 25 milions d'anys d'evolució i s'ha proposat un model evolutiu amb reordenaments específics i mecanismes de generació. Correlacions clínico-moleculars en els pacients amb la SWB han permès determinar que l'haploinsuficiència per NCF1, un gen localitzat a les duplicacions, és un factor protector per hipertensió. S'ha proposat un model patogènic per la hipertensió, implicant l'oxidasa NAD(P)H i estrès oxidatiu, suggerint que noves estratègies terapèutiques podrien ser utilitzades. A més, s'ha caracteritzat parcialment la funció de GTF2IRD2, un altre gen de les duplicacions. GTF2IRD2 interacciona amb altres factors de transcripció relacionats, té una localització subcel·lular variable i no s'uneix a ADN. Aquests resultats contribueixen a conèixer millor els mecanismes mutacionals i patogènics de la SWB. / This work presents the molecular evolution along with the functional analysis of the genes located in the segmental duplications flanking the 7q11.23 region, involved in Williams-Beuren syndrome (WBS). The generation of the segmental duplications has been dated to the last 25 million years of evolution and an evolutionary model with specific rearrangements and mechanisms has been proposed. Clinical-molecular correlations in WBS patients have allowed to determine that haploinsufficiency at NCF1, a gene located in the duplications, is a protective factor for hypertension. A pathogenic model for hypertension has been proposed, implicating NAD(P)H oxidase and oxidative stress, and suggesting that novel therapeutic strategies could be used. In addition, the functional characterization of another gene of the duplications, GTF2IRD2, has been partially achieved. GTF2IRD2 has been shown to interact with other related transcription factors, to display variable subcellular localization and to lack DNA binding properties. These results contribute to a better knowledge of the mutational and pathogenic mechanisms of the WBS.