A perda dentária tem como consequência a atrofia óssea. Além disso, em regiões posteriores da maxila, a pneumatização do assoalho do seio maxilar (ASM) pode comprometer a instalação de implantes dentários em uma posição protética ideal. O objetivo deste estudo foi avaliar em imagens de tomografia computadorizada de feixe cônico (TCFC) a estimativa da pneumatização (EP) do ASM após perda dentária unitária em região posterior da maxila. 183 imagens de TCFC foram analisadas bilateralmente e divididas em 2 grupos: lado edêntulo (LE) - região edêntula unitária em segundo pré-molar, primeiro ou segundo molares superiores; lado dentado (LD) - região contralateral homóloga à região do LE, com dente presente. Os seguintes parâmetros foram avaliados para comparação LE versus LD: altura do seio (AS), desfecho primário, e área do seio maxilar (SM). A EP (diferença de AS do LE menos LD) e a altura do rebordo (AR - analisada apenas no LE) foram comparadas de acordo com tipo de dente e presença de pneumatização entre as raízes (PR) do LD. Além disso, o rebordo cicatrizado foi categorizado de acordo com a opção terapêutica para maxilar posterior. Os resultados mostraram que o LE apresentou a AS maior que o LD (p<0,05) (6,90 ± 3,15 mm e 6,0 ± 3,01 mm, para LE e LD respectivamente e a EP de 0,9 ± 2,93 mm). Ao separar EP por tipo de dente observou-se que os segundos pré-molares e segundos molares apresentaram valores próximos (1,36 ± 2,43 e 1,21 ± 2,98 mm, respectivamente), enquanto que os primeiros molares apresentaram valores menores (0,55 ± 3,03 mm) (p>0,05). Ao separar os dados de EP de acordo com a presença da pneumatização no LD, observou-se que a maioria dos dentes com esta condição foram os primeiros molares (36 em 43). A EP na presença dessa condição foi de -0,26 ± 2,82 mm, enquanto que na ausência de PR, a EP foi de 1,22 ± 2,99 (p<0,05). Em relação aos parâmetros da crista alveolar, o rebordo cicatrizado apresentou menor altura que às cristas alveolares palatina e vestibular. 54% dos casos de molares que apresentaram pneumatização entre as raízes obtiveram AR < 5mm, sugerindo necessidade de enxerto para uma futura instalação de implante dentário. Portanto, podemos concluir que perdas dentárias em região posterior de maxila favorecem a pneumatização do ASM e que esta varia de acordo com o tipo de dente. Além disso, a identificação de pneumatização entre as raízes parece indicar uma maior tendência à necessidade de cirurgias de levantamento de seio. / The aim of this study was to evaluate the estimation of MSF pneumatization (EP) after single tooth loss in the posterior maxilla region in cone beam computed tomography (CBCT) images. 183 CBCT images were analyzed bilaterally and divided into 2 groups: edentulous side (ES) - edentulous single region in the maxillary second premolar, first or second molars; Tooth side (TS) - contralateral region homologous to the ES region, with tooth present. The following parameters were evaluated for ES vs TS: sinus height (SH), primary outcome, and maxillary sinus area (MSA). The EP (SH difference between ES and TS) and ridge height (RH - analyzed only in ES) were compared according to tooth type and the presence of pneumatization between roots (PR) in TS. In addition, the healed ridge was categorized according to the therapeutic option for posterior maxilla. The results showed that the ES presented a higher SH than the TS (p <0.001) (6.90 ± 3.15 mm and 6.0 ± 3.01 mm for ES and TS respectively, and the EP of 0.9 ± 2.93 mm). When separating EP by tooth type, it was observed that the second premolars and second molars presented close values (1.36 ± 2.43 and 1.21 ± 2.98 mm, respectively), whereas the first molars presented minor values (0.55 ± 3.03 mm) (p>0.001). When separating the PR data according to the presence of pneumatization in the TS, it was observed that the majority of the teeth with this condition were the first molars (36 in 43). PE in the presence of this condition was -0.26 ± 2.82 mm, whereas in the absence of PR, the PE was 1.22 ± 2.99 (p <0.001). Regarding the parameters of the alveolar ridge, the healed ridge presented lower height than the palatal and vestibular alveolar ridges. 54% of the cases of molars that presented pneumatization between the roots obtained RH < 5mm, suggesting the need of grafting for a future installation of dental implant. Therefore, we can conclude that tooth loss in the maxillary posterior region favors the pneumatization of the MSF and it varies according to the type of tooth. In addition, the identification of pneumatization between the roots seems to indicate a greater tendency to the need for sinus lift surgeries.

L’ectoderme embryonnaire devient spécifié en ectoderme non-neural, plaque neurale et bordure neurale à la fin de la gastrulation. Les cellules de bordure neurale sont les progéniteurs de la crête neurale et des placodes. La crête neurale est une population transitoire de cellules multipotentes, qui se forme au cours de la neurulation. Quand les bourrelets neuraux s’élèvent pour former le tube neural, les cellules de la crête neurale subissent une transition épithélio-mésenchymateuse, migrent dans l'ensemble du corps pour atteindre leur destination finale et se différencier. La crête neurale donne naissance à de multiples dérivés tels que les neurones et les cellules gliales du système nerveux périphérique, le cartilage et les os du visage, ou encore les mélanocytes. Des régulations complexes, impliquant de nombreuses signalisations et la transcription de gènes-clé, orchestrent ces événements. Cependant, les premières étapes menant à la formation de la crête neurale et à la spécification précoce de la bordure neurale sont encore peu comprises. Nous avons analysé le transcriptome de la crête neurale d'embryon de l'amphibien Xenopus laevis, à la recherche de nouveaux régulateurs des premières étapes de la formation de la crête neurale. Nous avons constaté que le régulateur de la glycolyse PFKFB4, est exprimé dans l’ectoderme dorsal de la jeune gastrula et dans les cellules de la crête neurale. Ici, nous démontrons que PFKFB4 régule la spécification de l’ectoderme via la voie de signalisation Akt, indépendamment de la glycolyse, démontrant ainsi la première fonction non-glycolytique des enzymes PFKFB. En outre, cette régulation est essentielle pour permettre aux progéniteurs de l'ectoderme d’être spécifiés en plaque neurale, crête neurale, placodes ou ectoderme non neural, mettant en évidence un nouveau point de contrôle de développement. De plus, nous démontrons que PFKFB4 régule des étapes ultérieures de la formation de la crête neurale. Notre travail met en évidence que les régulateurs du métabolisme cellulaire possèdent des fonctions non-métaboliques pour contrôler des étapes de développement au cours du développement embryonnaire. / Embryonic ectoderm becomes specified into non-neural ectoderm, neural plate and neural border at the end of gastrulation. Neural border cells are the progenitors of the neural crest and placodes. The neural crest is a transient population of multipotent cells, which forms during neurulation. As the neural border elevates to form the neural tube, neural crest cells undergo an epithelial to mesenchymal transition, migrate extensively into the whole body to reach their final destinations and differentiate. Neural crest gives rise to multiple derivatives such as neurons and glia, facial cartilage, bones, melanocytes and sympatho-adrenal cells. A complex interplay of signaling and transcriptional regulations orchestrates these early patterning events. However, the first steps leading to NC formation and early specification at the NB are less understood. We analysed the NC transcriptome of frog embryos, to look for novel regulators of the early steps of NC formation. We found that the well-known glycolysis regulator PFKFB4, is expressed in early gastrula dorsal ectoderm, and in neurula neural crest cells. Here, we demonstrate that PFKFB4 regulates ectoderm specification via Akt signaling independently of glycolysis, thus demonstrating the first non-glycolytic function of PFKFB enzymes. Moreover, this regulation is essential to allow ectoderm embryonic progenitors to be patterned into neural plate, neural crest, placodes and definitive ectoderm, highlighting a novel developmental checkpoint. Moreover, we also demonstrate that PFKFB4 regulates later steps of neural crest formation. Our work highlights that regulators of cell metabolism accumulate non-metabolic related functions to control developmental steps during embryonic development.

In this study, the semi-empirical approach is introduced to accurately estimate the probability distribution of complex non-linear random variables in the field of wavestructure interaction. The structural form of the semi-empirical distribution is developed based on a mathematical representation of the process and the model parameters are estimated directly from utilization of the sample data. Here, three probability distributions are developed based on the quadratic transformation of the linear random variable. Assuming that the linear process follows a standard Gaussian distribution, the three-parameter Gaussian-Stokes model is derived for the second-order variables. Similarly, the three-parameter Rayleigh-Stokes model and the four-parameter Weibull- Stokes model are derived for the crests, troughs, and heights of non-linear process assuming that the linear variable has a Rayleigh distribution or a Weibull distribution. The model parameters are empirically estimated with the application of the conventional method of moments and the newer method of L-moments. Furthermore, the application of semi-empirical models in extreme analysis and estimation of extreme statistics is discussed. As a main part of this research study, the sensitivity of the model statistics to the variability of the model parameters as well as the variability in the samples is evaluated. In addition, the sample size effects on the performance of parameter estimation methods are studied. Utilizing illustrative examples, the application of semi-empirical probability distributions in the estimation of probability distribution of non-linear random variables is studied. The examples focused on the probability distribution of: wave elevations and wave crests of ocean waves and waves in the area close to an offshore structure, wave run-up over the vertical columns of an offshore structure, and ocean wave power resources. In each example, the performance of the semi-empirical model is compared with appropriate theoretical and empirical distribution models. It is observed that the semi-empirical models are successful in capturing the probability distribution of complex non-linear variables. The semi-empirical models are more flexible than the theoretical models in capturing the probability distribution of data and the models are generally more robust than the commonly used empirical models.

Η ακεραιότητα και η λειτουργία της μιτωτικής συσκευής διαδραματίζει ουσιώδη ρόλο για τον ορθό προσανατολισμό και την ολίσθηση των χρωμοσωμάτων στους πόλους της ατράκτου, οδηγώντας στον ισομερή διαχωρισμό των χρωμοσωμάτων κατά τη μιτωτική ή μειωτική διαίρεση. Τροποποιήσεις του δικτύου των μικροσωληνίσκων (α- και β-τουμπουλίνη) και των κέντρων οργάνωσης αυτών (ΜΤΟC, γ-τουμπουλίνη) είναι δυνατόν να προκαλέσουν βλάβες στη μιτωτική συσκευή, διαταράσσοντας το χρωμοσωματικό αποχωρισμό, με αποτέλεσμα το σχηματισμό ανευπλοειδικών κυττάρων. Η διουρητική φαρμακευτική ένωση υδροχλωροθειαζίδιο (HCTZ) χορηγείται κατά της υπέρτασης και είναι γνωστό ότι προκαλεί μη αποχωρισμό σε διπλοειδή στελέχη του μύκητα Aspergillus nidulans. Πρόσφατες μελέτες της ερευνητικής μας ομάδας έχουν δείξει ότι επάγει αυξημένες συχνότητες μικροπυρήνων και διαταράσσει το χρωμοσωματικό αποχωρισμό σε καλλιέργειες ανθρωπίνων λεμφοκυττάρων in vitro. Στην παρούσα εργασία μελετήθηκε η επίδραση του HCTZ στην οργάνωση του δικτύου των μικροσωληνίσκων κατά τη μεσόφαση και τη μίτωση, με συνδυασμένη εφαρμογή μεθόδων διπλής ανοσοσήμανσης των πρωτεϊνών των μικροσωληνίσκων, του κεντροσώματος και του κινητοχώρου. Εφαρμόστηκε επίσης in situ υβριδοποίηση με φθοροχρώματα (FISH), με α-satellite πανκεντρομερικό ανιχνευτή, για τον εντοπισμό μη ενσωματωμένου (lagging) χρωμοσωματικού υλικού. Η μελέτη πραγματοποιήθηκε σε κυτταρικές σειρές μυός C2C12 και ανθρώπου HFFF2. Παρατηρήθηκε ότι το HCTZ προκαλεί μείωση του ρυθμού διαίρεσης, αποδιοργάνωση του δικτύου των μικροσωληνίσκων και αυξημένη συχνότητα ανώμαλων μεταφάσεων με ποικίλο αριθμό σημάτων γ-τουμπουλίνης. Αυξάνει το ποσοστό των μεταφάσεων και μειώνει το ποσοστό των ανα-τελοφάσεων, προκαλώντας συσσώρευση των κυττάρων στο στάδιο της μετάφασης. Επίσης, επάγει τη χρωμοσωματική καθυστέρηση, καθώς αυξάνει τη συχνότητα των μικροπυρήνων που παρουσιάζουν τόσο σήμα κινητοχώρου όσο και σήμα κεντρομέρους. Η γενετική δράση του στα κύτταρα C2C12 δε φαίνεται να επηρεάζεται σημαντικά από τη χρονική διάρκεια έκθεσης των κυττάρων σ’ αυτό. Από τις δυο κυτταρικές σειρές που χρησιμοποιήθηκαν φαίνεται ότι τα κύτταρα C2C12 είναι περισσότερο ευαίσθητα στην απόκριση στο HCTZ. Τα αποτελέσματα μας, υποδεικνύουν ανευπλοειδογόνο δράση της φαρμακευτικής ένωσης, επιβεβαιώνοντας και ενισχύοντας προηγούμενα ευρήματα της ερευνητικής μας ομάδας. / The integrity and function of mitotic apparatus play essential role for the equitable orientation and the slipping of chromosomes to the spindle poles, indicating normal distribution of chromosomes during mitotic or meiotic division. Modifications of the microtubule network (α- and β- tubulin) and microtubule-organizing centers (MTOC, γ- tubulin) may cause severe damage to the mitotic apparatus, disturbing the segregation of chromosomes and resulting to aneuploid cells. The diuretic drug hydrochlorothiazide (HCTZ) is used for the treatment of hypertension and has been found to induce non-disjunction in diploid strains of Aspergillus nidulans. Recent studies of our team have shown that HCTZ produces increased frequencies of micronuclei and disturbs chromosome segregation in human lymphocytes cultures treated in vitro. In the present study was investigated the effect of HCTZ on the organization of the microtubule network during mesophase and mitosis, with combined application of double immunofluorescence staining assay, for the visualization of microtubules, centrosomes and kinetochore proteins. Fluorescence in situ hybridization (FISH), with α-satellite pancentromeric probe, was also applied, for the localization of not integrated (lagging) nuclear material. The study was realized in C2C12 mouse cells and HFFF2 human cells. Our results revealed that HCTZ causes decrease of the cell division rate, disorganization of the microtubule network and increased frequency of abnormal metaphases with various γ-tubulin signals. HCTZ increases the percentage of metaphases and decreases the percentage of ana-telophases, indicating a metaphase arrest. Also, induces chromosome delay, as was shown from the high frequency of micronuclei that presents kinetochore and centromere signal. The genetic activity of HCTZ in C2C12 cells does not appear to be significantly influenced by the duration of the cell’s exposure time to the drug. It appears that C2C12 mouse cells are more sensitive in their response to the HCTZ. These results indicate aneugenic activity of this drug, confirming and enhancing our previous findings.

One of the most controversial and dramatic features of recent city development is the phenomenon of access to land through informal means, which is a reflection of the lack of alternative delivery systems. Constraints on the supply of land for housing the urban poor have resulted in a large housing backlog, reSUlting in overcrowding, the emergence of unplanned housing such as backyard shacks and free standing informal settlements. In South Africa, the majority of the popUlation who have been historically constrained by racist and restrictive land allocation processes found it difficult to access well located and affordable serviced land. These constraints have resulted in poor people obtaining access to land through informal delivery systems. This effective exclusion of the urban poor from the formal land market has resulted in the emergence of the informal systems of land delivery, such as land invasions etc. Both internationally and in South Africa, informal settlements and squatting have represented a way of addressing and challenging market relations and state regUlation and thus, allow for poorer people to move into better located areas. The existing informal settlement within the Cato Manor area (Cato Crest) can be regarded as an example of this kind of urban process. The purpose of this dissertation is to assess the performance of the informal delivery systems in Cato Crest, to establish whether these systems have reached the urban poor and to look for ways of dealing with informal land mechanisms in the future. The findings from the survey indicated that in Cato Crest these illegal land supply systems have benefitted poor people in terms of job opportunities, proximity to the city and location. A number of recommendations can be made in this regard: that there is a need for a land policy on informal land supply systems, that which should seek to make strategically located land available for low income housing in the future. If this is not accomplished, illegal land occupation will continue unabated until no land will be available for low income housing. / Thesis (M.Sc.U.R.P.)-University of Natal, Durban, 1995.

Eph receptors and their ephrin ligands play important roles in guiding mouse and Xenopus cranial neural crest (CNC) cells to their destinations. My objective was to determine if Ephs and ephrins also regulate avian CNC pathfinding. By double labeling for Eph or ephrin RNA and a neural crest marker protein, I was able to clearly distinguish neural crest from ectoderm and head mesenchyme and show that avian CNC cells express EphA3, 4, and 7 and EphB 1 and 3 and migrate along pathways bordered by non-neural crest cells expressing ephrin-B 1. Surprisingly, avian CNC cells also express ephrin-B2 and migrate along pathways bordered by non-neural crest cells expressing EphB2. Consistent with these findings, explanted avian CNC cells are labeled by both ephrin-B I and EphB2 Fc fusion proteins. Given the choice between growing out onto substrate-bound fibronectin (FN) or FN plus clustered Fc protein in the stripe assay, these cells show no preference for either condition. Conversely, given the choice between FN or FN plus clustered ephrin-B1 or EphB2 Fc fusion protein, the cells strongly localize to stripes containing only FN. This response is mitigated in the presence of soluble ephrin-B1/Fc or EphB2/Fc, but not in the presence of soluble Fc alone. These findings show that avian CNC cells have a mutually exclusive distribution with non-neural crest cells expressing ephrin-B 1 and EphB2 RNA in situ and are repelled from ephrin-B1 and EphB2 protein in vitro, suggesting that their migration is guided by both forward signaling through a variety of Eph receptors as stimulated by ephrin-B1 and reverse signaling through ephrin-B2 as stimulated by EphB2. I further explore the phylogeny of Ephs and ephrins and show that these genes diversified at different times in evolutionary history, such that the ancestral chordate likely had a single receptor for two different ligands.

Thesis (Ph. D.) -- University of Texas Southwestern Medical Center at Dallas, 2003. / Vita. Bibliography: References located at the end of each chapter.

Eph receptors and their ephrin ligands play important roles in guiding mouse and Xenopus cranial neural crest (CNC) cells to their destinations. My objective was to determine if Ephs and ephrins also regulate avian CNC pathfinding. By double labeling for Eph or ephrin RNA and a neural crest marker protein, I was able to clearly distinguish neural crest from ectoderm and head mesenchyme and show that avian CNC cells express EphA3, 4, and 7 and EphB 1 and 3 and migrate along pathways bordered by non-neural crest cells expressing ephrin-B 1. Surprisingly, avian CNC cells also express ephrin-B2 and migrate along pathways bordered by non-neural crest cells expressing EphB2. Consistent with these findings, explanted avian CNC cells are labeled by both ephrin-B I and EphB2 Fc fusion proteins. Given the choice between growing out onto substrate-bound fibronectin (FN) or FN plus clustered Fc protein in the stripe assay, these cells show no preference for either condition. Conversely, given the choice between FN or FN plus clustered ephrin-B1 or EphB2 Fc fusion protein, the cells strongly localize to stripes containing only FN. This response is mitigated in the presence of soluble ephrin-B1/Fc or EphB2/Fc, but not in the presence of soluble Fc alone. These findings show that avian CNC cells have a mutually exclusive distribution with non-neural crest cells expressing ephrin-B 1 and EphB2 RNA in situ and are repelled from ephrin-B1 and EphB2 protein in vitro, suggesting that their migration is guided by both forward signaling through a variety of Eph receptors as stimulated by ephrin-B1 and reverse signaling through ephrin-B2 as stimulated by EphB2. I further explore the phylogeny of Ephs and ephrins and show that these genes diversified at different times in evolutionary history, such that the ancestral chordate likely had a single receptor for two different ligands.

Foi desenvolvido projeto de pesquisa clínica e radiográfica para avaliar a influência do ângulo formado entre a superfície dental e a crista óssea na determinação da profundidade de sondagem do sulco gengival e complementarmente no comportamento da margem gengival por vestibular de dentes molares inferiores inclinados para mesial. Para tanto foram incluídos 30 sítios mesiais e 30 distais no grupo teste, com igual número de sítios controles de molares inferiores com inclinação normal. Nos dentes que forneceram esses sítios também foi feita a determinação da profundidade do sulco gengival na região vestibular central do dente, identificando-se a qualidade e quantidade de gengiva ceratinizada, respectivamente pela metodologia de Kan et al. (2010) e pela mensuração com sonda periodontal da distância da margem gengival à junção mucogengival. Foram incluídos pacientes periodontal e sistemicamente saudáveis, excluindo-se pacientes que tivessem sido submetidos a procedimentos ósseos regenerativos prévios nas áreas de interesse, diabéticos relutantes ao controle médico, usuários de drogas e/ou álcool, portadores de alterações sistêmicas que interfiram no metabolismo ósseo (como por exemplo, osteoporose e hiperparatireoidismo). Os exames foram realizados por examinador competente, devidamente calibrado. Para análise radiográfica as imagens foram transferidas para o computador, realizando-se as mensurações dos ângulos interessados com o programa de computador MB-Ruler Pro (MB-Software solutions). A análise estatística foi realizada no programa GraphPad Prism versão 5.03 para Windows (GraphPad, Usa). Os resultados obtidos em linhas gerais mostraram que houve influência significativa do ângulo entre a superfície dental e a crista óssea (p > 0,0001) na determinação do sulco gengival proximal em áreas de dentes inclinados, porém não há essa influência na profundidade de sondagem do sulco gengival por vestibular para áreas com qualidade e quantidade de gengiva comparáveis ao controle (p=0,08). A despeito desses resultados, não se encontrou correlação definida entre nenhum dos parâmetros de interesse analisados. Dentro dos limites do estudo os resultados também evidenciaram que, embora possam ocorrer variações desses parâmetros, a saúde periodontal pode ser mantida pelo indivíduo nas condições analisadas. / A clinical and radiographic research project was developed to assess the influence of the angle formed between the tooth surface and the alveolar bone crest in determining the probing depth of the gingival sulcus and complementary also to evaluate the behavior of the buccal gingival margin of mesially inclined molars. Therefore, 30 mesial and 30 distal sites of inclined lower molars were included in the test group, with an equal number of sites of lower molars with normal inclination in the control group. In addition in all the teeth of both test and control groups the depth of the clinical gingival sulcus at the central buccal region of the tooth was assessed by measuring with a periodontal probe, identifying the quality of the keratinized gingiva through the methodology of Kan et al. (2010) and determining the width of keratinized gingiva by measuring the distance from the free gingival margin to the mucogingival junction. The study was done in systemic and periodontally healthy individuals, excluding patients who had undergone bone-regenerative procedures in the areas of interest, diabetics reluctant to medical control, alcohol and / or drug users, and individuals suffering from systemic conditions that might interfere with bone metabolism (like osteoporosis and hyperparathyroidism). The examinations were performed by a competent and properly calibrated examiner. The radiographic images were then transferred to a computer in order to analyze the measurements of the involved angles with the computer program MB-Ruler Pro (MB-Software solutions). Statistical analysis was performed using GraphPad Prism version 5.03 for Windows (GraphPad, Usa). The results in general showed that there was significant influence of the angle between the tooth surface and the alveolar bone crest on the depth of the gingival sulcus in proximal areas of inclined teeth (p > 0,0001), but there was no such influence in the probing depth of the buccal gingival sulcus of these inclined molars provided that the quality and quantity of gingiva were similar to controls comprised by molars with normal inclination (p=0,08). Despite this significance, there was no definite correlation between any of the analyzed parameters of interest. The results also showed that, although there may be variations of these parameters, within the limits of this study the conditions of periodontal health can be maintained by the individual.

Le système nerveux entérique (SNE) provient des cellules de crête neurale entériques (CCNEs) qui migrent au sein de l'intestin embryonnaire, prolifèrent et se différencient en cellules gliales et neurones formant des ganglions interconnectés. Mon projet de thèse vise à comprendre comment les propriétés biochimiques et mécaniques de l'intestin embryonnaire influencent la colonisation et la différenciation des ccnes. L'absence d'endothéline-3 (EDN3), un facteur biochimique exprimé dans la paroi intestinale, est une des causes de la maladie de hirschsprung, caracterisée par une aganglionose du côlon distal. Nous montrons pour la première fois que l'EDN3 stimule l'adhésivité des CCNEs en augmentant leurs adhérences focales dépendantes des intégrines beta1 ainsi que la dynamique de leurs protrusions membranaires. De plus, nous avons mis en évidence l'existence d'une interaction génétique entre Edn3 et Itgb1 gouvernant le développement du SNE. Par ailleurs, les propriétés mécaniques du microenvironnement influençant la migration et la différenciation cellulaire , nous avons analysé par des approches biophysiques les propriétés élastiques de l'intestin embryonnaire et leurs impacts sur les comportements des ccnes. Nous avons montré que l'intestin embryonnaire se rigidifie au cours de son developpement et que la migration en 3D des CCNEs est inhibée lorsque la rigidité de l'environnement dépasse un certain seuil. Enfin, nous avons démarré l'analyse de l'effet de l'élasticité sur la différenciation des progéniteurs entériques. L'ensemble de nos résultats permettent de mieux comprendre les mécanismes contrôlant le développement du SNE. / The enteric nervous system (ENS) is derived from enteric neural crest cells (ENCC) that migrate along the length of the intestine through the gut mesenchyme. During this process, ENCC proliferate and differentiate into glial cells and neurons, which aggregate into ganglia. The aim of my thesis is to study how biochemical and mechanical properties of the gut tissue influence ENCC colonization and fate during embryogenesis. The absence of endothelin-3 (EDN3), a small peptide trapped in the embryonic gut mesenchyme, is one of the causes leading to hirschsprung disease, characterized by an aganglionosis of the distal colon. We highlighted for the first time that EDN3 increases ENCC adhesion properties throught 1-integrins focal adhesions and modulates their protrusion dynamics. Moreover, we evidenced a genetic interaction between Edn3 and Itgb1 during ENS development. Also, it is now well established that mechanical properties of the microenvironment influence fundamental mechanisms such as cell migration and cell fate determination. Thus, we analysed whether the mechanical properties of the ENCC’s environment influence their behaviours. Using biophysical approaches, we evidenced a physiological stiffening of the embryonic gut during its development and showed that ENCC migration in 3D is inhibited above a certain rigidity threshold. Finally, we begun to analyse the influence of the elastic properties of the environment onto enteric progenitor cells differenciation, taking advantage of the neurosphere culture system. All together, our results contribute to the understanding of the molecular and cellular mechanisms driving physiological and pathological ENS ontogenesis.