Glucocorticoid-induced tumor necrosis factor receptor is a p21Cip1/WAF1 transcriptional target conferring resistance of keratinocytes to UV light-induced apoptosis.

Glucocorticoid-induced tumor necrosis factor receptor (GITR) is a member of the tumor necrosis factor receptor superfamily, is expressed in T lymphocytes, and exerts an anti-apoptotic function in these cells. We reported that GITR is also highly expressed in the skin, specifically in keratinocytes, and that it is under negative transcriptional control of p21(Cip1/WAF1), independently from the cell cycle. Although GITR expression is higher in p21-deficient keratinocytes and skin, it is down-modulated with differentiation and in response to UVB. The combined analysis of keratinocytes with increased GITR expression versus normal keratinocytes and skin of mice with a disruption of the GITR gene indicates that this protein protects keratinocytes from UVB-induced apoptosis both in vitro and in vivo.

Recent advances in the epidermal growth factor receptor/ligand system biology on skin homeostasis and keratinocyte stem cell regulation.

The epidermal growth factor (EGF) receptor/ligand system stimulates multiple pathways of signal transduction, and is activated by various extracellular stimuli and inter-receptor crosstalk signaling. Aberrant activation of EGF receptor (EGFR) signaling is found in many tumor cells, and humanized neutralizing antibodies and synthetic small compounds against EGFR are in clinical use today. However, these drugs are known to cause a variety of skin toxicities such as inflammatory rash, skin dryness, and hair abnormalities. These side effects demonstrate the multiple EGFR-dependent homeostatic functions in human skin. The epidermis and hair follicles are self-renewing tissues, and keratinocyte stem cells are crucial for maintaining these homeostasis. A variety of molecules associated with the EGF receptor/ligand system are involved in epidermal homeostasis and hair follicle development, and the modulation of EGFR signaling impacts the behavior of keratinocyte stem cells. Understanding the roles of the EGF receptor/ligand system in skin homeostasis is an emerging issue in dermatology to improve the current therapy for skin disorders, and the EGFR inhibitor-associated skin toxicities. Besides, controlling of keratinocyte stem cells by modulating the EGF receptor/ligand system assures advances in regenerative medicine of the skin. We present an overview of the recent progress in the field of the EGF receptor/ligand system on skin homeostasis and regulation of keratinocyte stem cells.

Ultraweak photon emission in assessing bone growth factor efficiency using fibroblastic differentiation.

Photons participate in many atomic and molecular interactions and changes. Recent biophysical research has shown the induction of ultraweak photons in biological tissue. It is now established that plants, animal and human cells emit a very weak radiation which can be readily detected with an appropriate photomultiplier system. Although the emission is extremely low in mammalian cells, it can be efficiently induced by ultraviolet light. In our studies, we used the differentiation system of human skin fibroblasts from a patient with Xeroderma Pigmentosum of complementation group A in order to test the growth stimulation efficiency of various bone growth factors at concentrations as low as 5 ng/ml of cell culture medium. In additional experiments, the cells were irradiated with a moderate fluence of ultraviolet A. The different batches of growth factors showed various proliferation of skin fibroblasts in culture which could be correlated with the ultraweak photon emission. The growth factors reduced the acceleration of the fibroblast differentiation induced by mitomycin C by a factor of 10-30%. In view that fibroblasts play an essential role in skin aging and wound healing, the fibroblast differentiation system is a very useful tool in order to elucidate the efficacy of growth factors.

Oxygen consumption of Litopenaeus vannamei juveniles in heterotrophic medium with zero water exchange

This work aimed at determining the dissolved oxygen consumption rate of Litopenaeus vannamei juveniles maintained in a microbial biofloc raceway system at high density with no aeration. Three 4 L bottles were filled for each treatment, sealed hermetically, and placed in an enclosed greenhouse raceway system. Four shrimp (13.2±1.42 g) were assigned to two sets of the bottles, which underwent the following treatments: light conditions with no shrimp; dark conditions with no shrimp; light conditions with shrimp; and dark conditions with shrimp. Dissolved oxygen content was measured every 10 min for 30 min. A quadratic behavior was observed in dissolved oxygen concentration over time. Significant differences for oxigen consumption were observed only at 10 and 20 min between shrimp maintained in the dark and those under light conditions. At 10 min, a higher value was observed in shrimp maintained under light, and at 20 min, in the dark. Significant differences between 10 and 20 min and between 10 and 30 min were observed when oxygen consumption was analyzed over time in the presence of light. Under dark conditions there were significant differences only between 20 and 30 min. Lethal oxygen concentration (0.65 mg L-1) would be reached in less than one hour either under light or dark conditions with no aeration.

Selective inhibition of JNK with a peptide inhibitor attenuates pain hypersensitivity and tumor growth in a mouse skin cancer pain model.

Cancer pain significantly affects the quality of cancer patients, and current treatments for this pain are limited. C-Jun N-terminal kinase (JNK) has been implicated in tumor growth and neuropathic pain sensitization. We investigated the role of JNK in cancer pain and tumor growth in a skin cancer pain model. Injection of luciferase-transfected B16-Fluc melanoma cells into a hindpaw of mouse induced robust tumor growth, as indicated by increase in paw volume and fluorescence intensity. Pain hypersensitivity in this model developed rapidly (<5 days) and reached a peak in 2 weeks, and was characterized by mechanical allodynia and heat hyperalgesia. Tumor growth was associated with JNK activation in tumor mass, dorsal root ganglion (DRG), and spinal cord and a peripheral neuropathy, such as loss of nerve fibers in the hindpaw skin and induction of ATF-3 expression in DRG neurons. Repeated systemic injections of D-JNKI-1 (6 mg/kg, i.p.), a selective and cell-permeable peptide inhibitor of JNK, produced an accumulative inhibition of mechanical allodynia and heat hyperalgesia. A bolus spinal injection of D-JNKI-1 also inhibited mechanical allodynia. Further, JNK inhibition suppressed tumor growth in vivo and melanoma cell proliferation in vitro. In contrast, repeated injections of morphine (5 mg/kg), a commonly used analgesic for terminal cancer, produced analgesic tolerance after 1 day and did not inhibit tumor growth. Our data reveal a marked peripheral neuropathy in this skin cancer model and important roles of the JNK pathway in cancer pain development and tumor growth. JNK inhibitors such as D-JNKI-1 may be used to treat cancer pain.

Functions of the peroxisome proliferator-activated receptor (PPAR) alpha and beta in skin homeostasis, epithelial repair, and morphogenesis.

The three peroxisome proliferator-activated receptors (PPAR alpha, PPAR beta, and PPAR gamma) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. They are regarded as being sensors of physiological levels of fatty acids and fatty acid derivatives. In the adult mouse skin, they are found in hair follicle keratinocytes but not in interfollicular epidermis keratinocytes. Skin injury stimulates the expression of PPAR alpha and PPAR beta at the site of the wound. Here, we review the spatiotemporal program that triggers PPAR beta expression immediately after an injury, and then gradually represses it during epithelial repair. The opposing effects of the tumor necrosis factor-alpha and transforming growth factor-beta-1 signalling pathways on the activity of the PPAR beta promoter are the key elements of this regulation. We then compare the involvement of PPAR beta in the skin in response to an injury and during hair morphogenesis, and underscore the similarity of its action on cell survival in both situations.

Placental growth factor-1 and epithelial haemato-retinal barrier breakdown: potential implication in the pathogenesis of diabetic retinopathy.

AIMS/HYPOTHESIS: Disruption of the retinal pigment epithelial (RPE) barrier contributes to sub-retinal fluid and retinal oedema as observed in diabetic retinopathy. High placental growth factor (PLGF) vitreous levels have been found in diabetic patients. This work aimed to elucidate the influence of PLGF-1 on a human RPE cell line (ARPE-19) barrier in vitro and on normal rat eyes in vivo. METHODS: ARPE-19 permeability was measured using transepithelial resistance and inulin flux under stimulation of PLGF-1, vascular endothelial growth factor (VEGF)-E and VEGF 165. Using RT-PCR, we evaluated the effect of hypoxic conditions or insulin on transepithelial resistance and on PLGF-1 and VEGF receptors. The involvement of mitogen-activated protein kinase (MEK, also known as MAPK)/extracellular signal-regulated kinase (ERK, also known as EPHB2) signalling pathways under PLGF-1 stimulation was evaluated by western blot analysis and specific inhibitors. The effect of PLGF-1 on the external haemato-retinal barrier was evaluated after intravitreous injection of PLGF-1 in the rat eye; evaluation was by semi-thin analysis and zonula occludens-1 immunolocalisation on flat-mounted RPE. RESULTS: In vitro, PLGF-1 induced a reversible decrease of transepithelial resistance and enhanced tritiated inulin flux. These effects were specifically abolished by an antisense oligonucleotide directed at VEGF receptor 1. Exposure of ARPE-19 cells to hypoxic conditions or to insulin induced an upregulation of PLGF-1 expression along with increased transcellular permeability. The PLGF-1-induced RPE cell permeability involved the MEK signalling pathway. Injection of PLGF-1 in the rat eye vitreous induced an opening of the RPE tight junctions with subsequent sub-retinal fluid accumulation, retinal oedema and cytoplasm translocation of junction proteins. CONCLUSIONS/INTERPRETATION: Our results indicate that PLGF-1 may be a potential regulation target for the control of diabetic retinal and macular oedema.

Blood pressure-independent cardiac hypertrophy induced by locally activated renin-angiotensin system.

Cardiac hypertrophy is frequent in chronic hypertension. The renin-angiotensin system, via its effector angiotensin II (Ang II), regulates blood pressure and participates in sustaining hypertension. In addition, a growing body of evidence indicates that Ang II acts also as a growth factor. However, it is still a matter of debate whether the trophic effect of Ang II can trigger cardiac hypertrophy in the absence of elevated blood pressure. To address this question, transgenic mice overexpressing the rat angiotensinogen gene, specifically in the heart, were generated to increase the local activity of the renin-angiotensin system and therefore Ang II production. These mice develop myocardial hypertrophy without signs of fibrosis independently from the presence of hypertension, demonstrating that local Ang II production is important in mediating the hypertrophic response in vivo.

Identification of in vitro phosphorylation sites in the growth cone protein SCG10. Effect Of phosphorylation site mutants on microtubule-destabilizing activity.

SCG10 is a neuron-specific, membrane-associated protein that is highly concentrated in growth cones of developing neurons. Previous studies have suggested that it is a regulator of microtubule dynamics and that it may influence microtubule polymerization in growth cones. Here, we demonstrate that in vivo, SCG10 exists in both phosphorylated and unphosphorylated forms. By two-dimensional gel electrophoresis, two phosphoisoforms were detected in neonatal rat brain. Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A, Ser-62 and Ser-73 for mitogen-activated protein kinase and Ser-73 for cyclin-dependent kinase. We also show that overexpression of SCG10 induces a disruption of the microtubule network in COS-7 cells. By expressing different phosphorylation site mutants, we have dissected the roles of the individual phosphorylation sites in regulating its microtubule-destabilizing activity. We show that nonphosphorylatable mutants have increased activity, whereas mutants in which phosphorylation is mimicked by serine-to-aspartate substitutions have decreased activity. These data suggest that the microtubule-destabilizing activity of SCG10 is regulated by phosphorylation, and that SCG10 may link signal transduction of growth or guidance cues involving serine/threonine protein kinases to alterations of microtubule dynamics in the growth cone.

Nonactivated versus thrombin-activated platelets on wound healing and fibroblast-to-myofibroblast differentiation in vivo and in vitro.

Background: Platelet preparations for tissue healing are usually preactivated before application to deliver concentrated growth factors. In this study, the authors investigated the differences between nonactivated and thrombin-activated platelets in wound healing.Methods: The healing effects (i.e., wound closure, myofibroblast formation, and angiogenesis) of nonactivated and thrombin-activated platelets were compared in experimental wounds in diabetic (db/db) animals. In vitro, fibroblast phenotype and function were tested in response to platelets and activated platelets. No treatment served as a negative control.Results: Wounds treated with platelets reached 90 percent closure after 15 days, faster than activated platelets (26 days), and with higher levels of myofibroblasts and angiogenesis. In vitro, platelets enhanced cell migration and induced twofold higher myofibroblast differentiation and contraction compared with activated platelets.Conclusions: Platelets stimulate wound healing more efficiently compared with activated platelets by enhancing fibroblast differentiation and contractile function. Similar levels of growth factors may induce different biological effects when delivered "on demand" rather than in an initial bolus. (Plast. Reconstr. Surg. 129: 46e, 2012.)

Dissection of hormone-responsive plasma membrane to nucleus signaling of Bravis Radix : its role in vascular differentiation and root meristem growth

AbstractPlants continuously grow during their complete life span and understanding the mechanisms that qualitatively regulate their traits remains a challenging topic in biology. The hormone auxin has been identified as a crucial molecule for shaping plant growth, as it has a role in most developmental processes. In the root, the directional, so-called polar transport of auxin generates a peak of concentration that specifies and maintains the stem cell niche and a subsequent gradient of decreasing concentration that also regulates cell proliferation and differentiation. For these reasons, auxin is considered the main morphogen of the root, as it is fundamental for its organization and maintenance. Recently, in Arabidopsis thaliana, a natural variation screen allowed the discovery of BREVIS RADIX (BRX) gene as a limiting factor for auxin responsive gene expression and thus for root growth.In this study, we discovered that BRX is a direct target of auxin that positively feeds back on auxin signaling, as a transcriptional co-regulator, through interaction with the Auxin Response Factor (ARF) MONOPTEROS (MP), modulating the auxin gene response magnitude during the transition between division and differentiation in the root meristem. Moreover, we provide evidence that BRX is activated at the plasma membrane level as an associated protein before moving into the nucleus to modulate cellular growth.To investigate the discrepancy between the auxin concentration and the expression pattern of its downstream targets, we combined experimental and computational approaches. Expression profiles deviating from the auxin gradient could only be modeled after intersection of auxin activity with the observed differential endocytosis pattern and with positive auto- regulatory feedback through plasma- membrane-to-nucleus transfer of BRX. Because BRX is required for expression of certain auxin response factor targets, our data suggest a cell-type-specific endocytosis-dependent input into transcriptional auxin perception. This input sustains expression of a subset of auxin-responsive genes across the root meristem's division and transition zones and is essential for meristem growth. Thus, the endocytosis pattern provides specific positional information to modulate auxin response. RésuméLes plantes croissent continuellement tout au long de leur cycle de vie. Comprendre et expliquer les mécanismes impliqués dans ce phénomène reste à l'heure actuelle, un défi. L'hormone auxine a été identifiée comme une molécule essentielle à la régulation de la croissance des plantes, car impliquée dans la plupart des processus développementaux. Dans la racine, le transport polaire de l'auxine, par la génération d'un pic de concentration, spécifie et maintient la niche de cellules souches, et par la génération d'un gradient de concentration, contrôle la prolifération et la différentiation cellulaire. Puisque l'auxine est essentielle pour l'organisation et la maintenance du système racinaire, il est considéré comme son principal morphogène. Récemment, dans la plante modèle, Arabidopsis thalinana, un criblage des variations génétique a permis d'identifier le gène Brevis radix (BRX) comme facteur limitant l'expression des gènes de réponse à l'auxine et par là même, la croissance de la racine.Dans ce travail, nous avons découvert que BRX est une cible direct de l'auxine qui rétroactive positivement le signalement de l'hormone, agissant ainsi comme un régulateur transcriptionnel à travers l'interaction avec la protéine Monopteros (MP) de la famille des facteurs de réponse à l'auxine (Auxin Responsive Factor, ARF), et modulant ainsi la magnitude de la réponse des gènes reliés à l'auxine durant la division et la différentiation cellulaire dans le méristème de la racine. De plus, nous fournissons des preuves que BRX est activées au niveau de la membrane plasmique, tel une protéine associée se déplaçant à l'intérieur du noyau et modulant la croissance cellulaire.Pour mener à bien l'investigation des divergences entre la concentration de l'auxine et les schémas d'expression de ses propres gènes cibles, nous avons combiné les approches expérimentales et computationnelles. Les profiles d'expressions déviant du gradient d'auxine pourraient seulement être modéliser après intersection de l'activité de l'auxine avec les schémas différentiels d'endocytose observés et les boucles de rétroaction positives et autorégulatrices par le transfert de BRX de la membrane plasmique au noyau. Puisque BRX est requis pour l'expression de certains gènes cibles des facteurs de réponse à l'auxine, nos données suggèrent une contribution dépendante d'une endocytose spécifique au type de cellule dans la perception transcriptionnelle à l'auxine Cette contribution soutient l'expression d'un sous-set de gène de réponse à l'auxine dans la division du méristème racinaire et la zone de transition, et par conséquent, est essentielle pour la croissance méristematique. Ainsi, le schéma d'endocytose fournit des informations positionnelles spécifiques à la modulation de la réponse à l'auxine.

Growth promoting signaling by tenascin-C [corrected].

Tenascin-C is an adhesion-modulating extracellular matrix molecule that is highly expressed in tumor stroma and stimulates tumor cell proliferation. Adhesion of T98G glioblastoma cells to a fibronectin substratum is inhibited by tenascin-C. To address the mechanism of action, we performed a RNA expression analysis of T89G cells grown in the presence or absence of tenascin-C and found that tenascin-C down-regulates tropomyosin-1. Upon overexpression of tropomyosin-1, cell spreading on a fibronectin/tenascin-C substratum was restored, indicating that tenascin-C destabilizes actin stress fibers through down-regulation of tropomyosin-1. Tenascin-C also increased the expression of the endothelin receptor type A and stimulated the corresponding mitogen-activated protein kinase signaling pathway, which triggers extracellular signal-regulated kinase 1/2 phosphorylation and c-Fos expression. Tenascin-C additionally caused down-regulation of the Wnt inhibitor Dickkopf 1. In consequence, Wnt signaling was enhanced through stabilization of beta-catenin and stimulated the expression of the beta-catenin target Id2. Finally, our in vivo data derived from astrocytoma tissue arrays link increased tenascin-C and Id2 expression with high malignancy. Because increased endothelin and Wnt signaling, as well as reduced tropomyosin-1 expression, are closely linked to transformation and tumorigenesis, we suggest that tenascin-C specifically modulates these signaling pathways to enhance proliferation of glioma cells.

Rhythmic growth explained by coincidence between internal and external cues.

Most organisms use circadian oscillators to coordinate physiological and developmental processes such as growth with predictable daily environmental changes like sunrise and sunset. The importance of such coordination is highlighted by studies showing that circadian dysfunction causes reduced fitness in bacteria and plants, as well as sleep and psychological disorders in humans. Plant cell growth requires energy and water-factors that oscillate owing to diurnal environmental changes. Indeed, two important factors controlling stem growth are the internal circadian oscillator and external light levels. However, most circadian studies have been performed in constant conditions, precluding mechanistic study of interactions between the clock and diurnal variation in the environment. Studies of stem elongation in diurnal conditions have revealed complex growth patterns, but no mechanism has been described. Here we show that the growth phase of Arabidopsis seedlings in diurnal light conditions is shifted 8-12 h relative to plants in continuous light, and we describe a mechanism underlying this environmental response. We find that the clock regulates transcript levels of two basic helix-loop-helix genes, phytochrome-interacting factor 4 (PIF4) and PIF5, whereas light regulates their protein abundance. These genes function as positive growth regulators; the coincidence of high transcript levels (by the clock) and protein accumulation (in the dark) allows them to promote plant growth at the end of the night. Thus, these two genes integrate clock and light signalling, and their coordinated regulation explains the observed diurnal growth rhythms. This interaction may serve as a paradigm for understanding how endogenous and environmental signals cooperate to control other processes.

Mechanisms of garnet growth in eclogites of the Zermatt-Saas Fee unit, Western Alps

THESIS ABSTRACT Garnets are one of the key metamorphic minerals used to study peak metamorphic conditions or crystallization ages. Equilibrium is typically assumed between the garnet and the matrix. This thesis attempts to understand garnet growth in the Zermatt-Saas Fee (ZSF) eclogites, and discusses consequences for Sm/Nd and Lu/Hf dating and the equilibrium assumption. All studied garnets from the ZSF eclogites are strongly zoned in Mn, Fe, Mg, and Ca. Methods based on chemical zoning patterns and on 3D spatial statistics indicate different growth mechanisms depending on the sample studied. Garnets from the Pfulwe area are grown in a system where surface kinetics likely dominated over intergranular diffusion kinetics. Garnets fram two other localities, Nuarsax and Lago di Cignana, seem to have grown in a system where intergranular diffusion kinetics were dominating over surface kinetics, at least during initial growth. Garnets reveal strong prograde REE+Y zoning. They contain narrow central peaks for Lu + Yb + Tm ± Er and at least one additional small peak towards the rim. The REE Sm + Eu + Gd + Tb ± Dy are depleted in the cores but show one prominent peak close to the rim. It is shown that these patterns cam be explained using a transient matrix diffusion model where REE uptake is limited by diffusion in the matrix surrounding the porphyroblast. The secondary peaks in the garnet profiles are interpreted to reflect thermally activated diffusion due to a temperature increase during prograde metamorphism. The model predicts anomalously low 176Lu/177Hf and 147Sm/144Nd ratios in garnets where growth rates are fast compared to diffusion of the REE, which decreases garnet isochron precisions. The sharp Lu zoning was further used to constrain maximum Lu volume diffusion rates in garnet. The modeled minimum pre-exponential diffusion coefficient which fits the measured central peak is in the order of Do = 5.7* 106 m2/s, taking an activation energy of 270 kJ/mol. The latter was chosen in agreement with experimentally determined values. This can be used to estimate a minimum closure temperature of around 630°C for the ZSF zone. Zoning of REE was combined with published Lu/Hf and Sm/Nd age information to redefine the prograde crystallization interval for Lago di Cignana UHP eclogites. Modeling revealed that a prograde growth interval in the order of 25 m.y. is needed to produce the measured spread in ages. RÉSUMÉ Le grenat est un minéral métamorphique clé pour déterminer les conditions du pic de métamorphisme ainsi que l'âge de cristallisation. L'équilibre entre le grenat et la matrice est requis. Cette étude a pour but de comprendre la croissance du grenat dans les éclogites de la zone de Zermatt-Saas Fee (ZSF) et d'examiner quelques conséquences sur les datations Sm/Nd et Lu/Hf. Tous les grenats des éclogites de ZSF étudiés sont fortement zonés en Mn, Fe, Mg et partiellement en Ca. Les différentes méthodes basées sur le modèle de zonation chimique ainsi que sur les statistiques de répartition spatiale en 3D indiquent un mécanisme de croissance différent en fonction de la localité d'échantillonnage. Les grenats provenant de la zone de Pfulwe ont probablement crû dans un système principalement dominé par la cinétique de surface au détriment de 1a cinétique de diffusion intergranulaire. Les grenats provenant de deux autres localités, Nuarsax et Lago di Cignana, semblent avoir cristallisé dans un système dominé par la diffusion intergranulaire, au moins durant les premiers stades de croissance. Les grenats montrent une forte zonation prograde en Terres Rares (REE) ainsi qu'en Y. Les profils présentent au coeur un pic étroit en Lu + Yb+ Tm ± Er et au moins un petit pic supplémentaire vers le bord. Les coeurs des grenats sont appauvris en Sm + Eu + Gd + Tb ± Dy, mais les bords sont marqués par un pic important de ces REE. Ces profils s'expliquent par un modèle de diffusion matricielle dans lequel l'apport en REE est limité par la diffusion dans la matrice environnant les porphyroblastes. Les pics secondaires en bordure de grain reflètent la diffusion activée par l'augmentation de la température lors du métamorphisme prograde. Ce modèle prédit des rapports 176Lu/177Hf et 147Sm/144Nd anormalement bas lorsque les taux de croissance sont plus rapides que la diffusion des REE, ce qui diminue la précision des isochrones impliquant le grenat. La zonation nette en Lu a permis de contraindre le maximum de diffusion volumique par une approche numérique. Le coefficient de diffusion minimum modélisé en adéquation avec les pics mesurés est de l'ordre de Do = 5.7*10-6 m2/s, en prenant une énergie d'activation ~270 kJ/mol déterminée expérimentalement. Ainsi, la température de clôture minimale est estimée aux alentours de 630°C pour la zone ZSF. Des nouvelles données de zonation de REE sont combinées aux âges obtenus avec les rapports Lu/Hf et Sm/Nd qui redéfissent l'intervalle de cristallisation prograde pour les éclogites UHP de Lago di Cignana. La modélisation permet d'attribuer au minimum un intervalle de croissance prograde de 25 Ma afin d'obtenir les âges préalablement mesurés. RESUME GRAND PUBLIC L'un des principaux buts du pétrologue .métamorphique est d'extraire des roches les informations sur l'évolution temporelle, thermique et barométrique qu'elles ont subi au cours de la formation d'une chaîne de montagne. Le grenat est l'un des minéraux clés dans une grande variété de roches métamorphiques. Il a fait l'objet de nombreuses études dans des terrains d'origines variées ou lors d'études expérimentales afin de comprendre ses domaines de stabilité, ses réactions et sa coexistence avec d'autres minéraux. Cela fait du grenat l'un des minéraux les plus attractifs pour la datation des roches. Cependant, lorsqu'on l'utilise pour la datation et/ou pour la géothermobarométrie, on suppose toujours que le grenat croît en équilibre avec les phases coexistantes de la matrice. Pourtant, la croissance d'un minéral est en général liée au processus de déséquilibre. Cette étude a pour but de comprendre comment croît le grenat dans les éclogites de Zermatt - Saas Fee et donc d'évaluer le degré de déséquilibre. Il s'agit aussi d'expliquer les différences d'âges obtenues grâce aux grenats dans les différentes localités de l'unité de Zermatt-Saas Fee. La principale question posée lors de l'étude des mécanismes de croissance du grenat est: Parmi les processus en jeu lors de la croissance du grenat (dissolution des anciens minéraux, transport des éléments vers le nouveau grenat, précipitation d'une nouvelle couche en surface du minéral), lequel est le plus lent et ainsi détermine le degré de déséquilibre? En effet, les grenats d'une des localités (Pfulwe) indiquent que le phénomène d'adhérence en surface est le plus lent, contrairement aux grenats des autres localités (Lago di Cignana, Nuarsax) dans lesquels ce sont les processus de transport qui sont les plus lents. Cela montre que les processus dominants sont variables, même dans des roches similaires de la même unité tectonique. Ceci implique que les processus doivent être déterminés individuellement pour chaque roche afin d'évaluer le degré de déséquilibre du grenat dans la roche. Tous les grenats analysés présentent au coeur une forte concentration de Terres Rares: Lu + Yb + Tm ± Er qui décroît vers le bord du grain. Inversement, les Terres Rares Sm + Eu + Gd + Tb ± Dy sont appauvries au coeur et se concentrent en bordure du grain. La modélisation révèle que ces profils sont-dus à des cinétiques lentes de transport des Terres Rares. De plus, les modèles prédisent des concentrations basses en éléments radiogéniques pères dans certaines roches, ce qui influence fortement sur la précision des âges obtenus par la méthode d'isochrone. Ceci signifie que les roches les plus adaptées pour les datations ne doivent contenir ni beaucoup de grenat ni de très gros cristaux, car dans ce cas, la compétition des éléments entre les cristaux limite à de faibles concentrations la quantité d'éléments pères dans chaque cristal.