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1.
Gut ; 69(2): 380-392, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31076402

RESUMO

OBJECTIVE: Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors. microRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Given that miRNAs were indicated to regulate between 30% and 75% of all human genes, we aimed to investigate the functional and regulatory role of miRNAs for the HCV life cycle. DESIGN: To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV. miRNA targeting was then assessed using a combination of computational and functional approaches. RESULTS: We uncovered miR-501-3p and miR-619-3p as novel modulators of HCV assembly/release. We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity. Furthermore, increased OGT expression in patient-derived liver tissue was associated with HCV-induced liver disease and cancer. CONCLUSION: miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity. In addition to its effect on HCV morphogenesis, OGT may play a role in HCV-induced liver disease and hepatocarcinogenesis.


Assuntos
Hepacivirus/patogenicidade , Hepatite C Crônica/genética , N-Acetilglucosaminiltransferases/fisiologia , Regulação da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes/métodos , Estudo de Associação Genômica Ampla/métodos , Hepacivirus/fisiologia , Hepatite C Crônica/virologia , Hepatócitos/virologia , Interações Hospedeiro-Patógeno/genética , Humanos , Estágios do Ciclo de Vida/genética , MicroRNAs/genética , Morfogênese/fisiologia , N-Acetilglucosaminiltransferases/genética , Regulação para Cima , Virulência/genética
2.
Adv Exp Med Biol ; 1185: 495-499, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884660

RESUMO

Peripherin 2 (also known as RDS/Prph2) is localized to the rims of rod and cone outer segment (OS) discs. The C-terminus of Prph2 is a critical functional domain, but its exact role is still unknown. In this mini review, we describe work on the Prph2 C-terminus, highlighting its role as a regulator of protein trafficking, membrane curvature, ectosome secretion, and membrane fusion. Evidence supports a role for the Prph2 C-terminus in these processes and demonstrates that it is necessary for the initiation of OS morphogenesis.


Assuntos
Periferinas/fisiologia , Segmento Externo das Células Fotorreceptoras da Retina/fisiologia , Segmento Externo da Célula Bastonete/fisiologia , Humanos , Morfogênese , Transporte Proteico , Retina/crescimento & desenvolvimento
3.
BMC Evol Biol ; 19(1): 210, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722660

RESUMO

BACKGROUND: Many pathologies that modify the shell geometry and ornamentation of ammonoids are known from the fossil record. Since they may reflect the developmental response of the organism to a perturbation (usually a sublethal injury), their study is essential for exploring the developmental mechanisms of these extinct animals. Ammonoid pathologies are also useful to assess the value of some morphological characters used in taxonomy, as well as to improve phylogenetic reconstructions and evolutionary scenarios. RESULTS: We report on the discovery of an enigmatic pathological middle Toarcian (Lower Jurassic) ammonoid specimen from southern France, characterized by a pronounced left-right asymmetry in both ornamentation and suture lines. For each side independently, the taxonomic interpretations of ornamentation and suture lines are congruent, suggesting a Hildoceras semipolitum species assignment for the left side and a Brodieia primaria species assignment for the right side. The former exhibits a lateral groove whereas the second displays sinuous ribs. This specimen, together with the few analogous cases reported in the literature, lead us to erect a new forma-type pathology herein called "forma janusa" for specimens displaying a left-right asymmetry in the absence of any clear evidence of injury or parasitism, whereby the two sides match with the regular morphology of two distinct, known species. CONCLUSIONS: Since "forma janusa" specimens reflect the underlying developmental plasticity of the ammonoid taxa, we hypothesize that such specimens may also indicate unsuspected phylogenetic closeness between the two displayed taxa and may even reveal a direct ancestor-descendant relationship. This hypothesis is not, as yet, contradicted by the stratigraphical data at hand: in all studied cases the two distinct taxa correspond to contemporaneous or sub-contemporaneous taxa. More generally, the newly described specimen suggests that a hitherto unidentified developmental link may exist between sinuous ribs and lateral grooves. Overall, we recommend an integrative approach for revisiting aberrant individuals that illustrate the intricate links among shell morphogenesis, developmental plasticity and phylogeny.


Assuntos
Exoesqueleto/anatomia & histologia , Cefalópodes/anatomia & histologia , Fósseis , Animais , Evolução Biológica , Cefalópodes/classificação , França , Morfogênese , Filogenia
4.
Adv Exp Med Biol ; 1146: 31-44, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612452

RESUMO

Cells apply forces to their surroundings to perform basic biological activities, including division, adhesion, and migration. Similarly, cell populations in epithelial tissues coordinate forces in physiological processes of morphogenesis and repair. These activities are highly regulated to yield the correct development and function of the body. The modification of this order is at the onset of pathological events and malfunctions. Mechanical forces and their translation into biological signals are the focus of an emerging field of research, shaping as a central discipline in the study of life and gathering knowledge at the interface of engineering, physics, biology and medicine. Novel engineering methods are needed to complement the classic instruments developed by molecular biology, physics and medicine. These should enable the measurement of forces at the cellular and multicellular level, and at a temporal and spatial resolution which is fully compatible with the ranges experienced by cells in vivo.


Assuntos
Células Epiteliais , Animais , Fenômenos Biomecânicos , Movimento Celular , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Humanos , Morfogênese , Estresse Mecânico
5.
Adv Exp Med Biol ; 1146: 45-66, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612453

RESUMO

Collective cell migration plays a central role in tissue development, morphogenesis, wound repair and cancer progression. With the growing realization that physical forces mediate cell motility in development and physiology, a key biological question is how cells integrate molecular activities for force generation on multicellular scales. In this review we discuss recent advances in modeling collective cell migration using quantitative tools and approaches rooted in soft matter physics. We focus on theoretical models of cell aggregates as continuous active media, where the feedback between mechanical forces and regulatory biochemistry gives rise to rich collective dynamical behavior. This class of models provides a powerful predictive framework for the physiological dynamics that underlies many developmental processes, where cells need to collectively migrate like a viscous fluid to reach a target region, and then stiffen to support mechanical stresses and maintain tissue cohesion.


Assuntos
Fenômenos Biomecânicos , Movimento Celular , Modelos Biológicos , Movimento Celular/fisiologia , Morfogênese , Cicatrização
6.
Adv Exp Med Biol ; 1146: 105-116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612456

RESUMO

Collective cell migration is a key process in developmental biology, facilitating the bulk movement of cells in the morphogenesis of animal tissues. Predictive understanding in this field remains challenging due to the complexity of many interacting cells, their signalling, and microenvironmental factors - all of which can give rise to non-intuitive emergent behaviours. In this chapter we discuss biological examples of collective cell migration from a range of model systems, developmental stages, and spatial scales: border cell migration and haemocyte dispersal in Drosophila, gastrulation, neural crest migration, lateral line formation in zebrafish, and branching morphogenesis; as well as examples of developmental defects and similarities to metastatic invasion in cancer. These examples will be used to illustrate principles that we propose to be important: heterogeneity of cell states, substrate-free migration, contact-inhibition of locomotion, confinement and repulsive cues, cell-induced (or self-generated) gradients, stochastic group decisions, tissue mechanics, and reprogramming of cell behaviours. Understanding how such principles play a common, overarching role across multiple biological systems may lead towards a more integrative understanding of the causes and function of collective cell migration in developmental biology, and to potential strategies for the repair of developmental defects, the prevention and control of cancer, and advances in tissue engineering.


Assuntos
Movimento Celular , Morfogênese , Animais , Transdução de Sinais
7.
Nat Commun ; 10(1): 4710, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31624259

RESUMO

Morphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradients. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/ß-catenin signalling gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, identify that unfit cells with abnormal Wnt/ß-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/ß-catenin gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.


Assuntos
Padronização Corporal/genética , Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Morfogênese/genética , Via de Sinalização Wnt/genética , Proteínas de Peixe-Zebra/genética , beta Catenina/genética , Animais , Animais Geneticamente Modificados , Apoptose/genética , Embrião não Mamífero/citologia , Embrião não Mamífero/embriologia , Microscopia de Fluorescência , Imagem com Lapso de Tempo/métodos , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo , beta Catenina/metabolismo
8.
Nature ; 574(7776): 112-116, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31554966

RESUMO

Organogenesis is a complex and interconnected process that is orchestrated by multiple boundary tissue interactions1-7. However, it remains unclear how individual, neighbouring components coordinate to establish an integral multi-organ structure. Here we report the continuous patterning and dynamic morphogenesis of hepatic, biliary and pancreatic structures, invaginating from a three-dimensional culture of human pluripotent stem cells. The boundary interactions between anterior and posterior gut spheroids differentiated from human pluripotent stem cells enables retinoic acid-dependent emergence of hepato-biliary-pancreatic organ domains specified at the foregut-midgut boundary organoids in the absence of extrinsic factors. Whereas transplant-derived tissues are dominated by midgut derivatives, long-term-cultured microdissected hepato-biliary-pancreatic organoids develop into segregated multi-organ anlages, which then recapitulate early morphogenetic events including the invagination and branching of three different and interconnected organ structures, reminiscent of tissues derived from mouse explanted foregut-midgut culture. Mis-segregation of multi-organ domains caused by a genetic mutation in HES1 abolishes the biliary specification potential in culture, as seen in vivo8,9. In sum, we demonstrate that the experimental multi-organ integrated model can be established by the juxtapositioning of foregut and midgut tissues, and potentially serves as a tractable, manipulatable and easily accessible model for the study of complex human endoderm organogenesis.


Assuntos
Sistema Biliar/embriologia , Intestinos/embriologia , Fígado/embriologia , Modelos Biológicos , Morfogênese , Pâncreas/embriologia , Animais , Sistema Biliar/citologia , Biomarcadores/análise , Biomarcadores/metabolismo , Padronização Corporal , Endoderma/citologia , Endoderma/embriologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Intestinos/citologia , Fígado/citologia , Masculino , Camundongos , Organoides/citologia , Organoides/embriologia , Pâncreas/citologia , Esferoides Celulares/citologia , Esferoides Celulares/metabolismo , Esferoides Celulares/transplante , Fatores de Transcrição HES-1/análise , Fatores de Transcrição HES-1/metabolismo
9.
EMBO J ; 38(20): e102497, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31512749

RESUMO

Tissue morphogenesis in multicellular organisms is brought about by spatiotemporal coordination of mechanical and chemical signals. Extensive work on how mechanical forces together with the well-established morphogen signalling pathways can actively shape living tissues has revealed evolutionary conserved mechanochemical features of embryonic development. More recently, attention has been drawn to the description of tissue material properties and how they can influence certain morphogenetic processes. Interestingly, besides the role of tissue material properties in determining how much tissues deform in response to force application, there is increasing theoretical and experimental evidence, suggesting that tissue material properties can abruptly and drastically change in development. These changes resemble phase transitions, pointing at the intriguing possibility that important morphogenetic processes in development, such as symmetry breaking and self-organization, might be mediated by tissue phase transitions. In this review, we summarize recent findings on the regulation and role of tissue material properties in the context of the developing embryo. We posit that abrupt changes of tissue rheological properties may have important implications in maintaining the balance between robustness and adaptability during embryonic development.


Assuntos
Diferenciação Celular , Desenvolvimento Embrionário , Morfogênese , Reologia , Transdução de Sinais , Animais , Fenômenos Biomecânicos , Humanos
10.
Nat Cell Biol ; 21(10): 1191-1205, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31548610

RESUMO

Cells of multicellular organisms need to adopt specific morphologies. However, the molecular mechanisms bringing about membrane topology changes are far from understood-mainly because knowledge of membrane-shaping proteins that can promote local membrane curvatures is still limited. Our analyses unveiled that several members of a large, previously unrecognised protein family, which we termed N-Ank proteins, use a combination of their ankyrin repeat array and an amino (N)-terminal amphipathic helix to bind and shape membranes. Consistently, functional analyses revealed that the N-Ank protein ankycorbin (NORPEG/RAI14), which was exemplarily characterised further, plays an important, ankyrin repeat-based and N-terminal amphipathic helix-dependent role in early morphogenesis of neurons. This function furthermore required coiled coil-mediated self-assembly and manifested as ankycorbin nanodomains marked by protrusive membrane topologies. In summary, here, we unveil a class of powerful membrane shapers and thereby assign mechanistic and cell biological functions to the N-Ank protein superfamily.


Assuntos
Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/metabolismo , Morfogênese , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Animais , Repetição de Anquirina/genética , Células Cultivadas , Proteínas do Citoesqueleto/genética , Células HEK293 , Células HeLa , Humanos , Camundongos , Modelos Moleculares , Neurônios/citologia , Neurônios/metabolismo , Domínios Proteicos/genética , Ratos , Fatores de Transcrição/genética
11.
Histochem Cell Biol ; 152(6): 397-413, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31552487

RESUMO

The mechanisms that determine the commitment of thymic epithelial precursors to the two major thymic epithelial cell lineages, cTECs and mTECs, remain unknown. Here we show that FoxN1 nu mutation, which abolishes thymic epithelium differentiation, results in the formation of a tubular branched structure according to a typical branching morphogenesis and tubulogenesis developmental pattern. In the presence of FoxN1, in alymphoid NSG and fetal Ikaros-/- thymi, there is no lumen formation and only partial apical differentiation. This initiates cortex-medulla differentiation inducing expression of medullary genes in the apically differentiating cells and of cortical genes in the non-apically differentiating cells, which will definitely differentiate in wt and postnatal Ikaros-/- mice. Therefore, the thymus development is based on a branching morphogenesis and tubulogenesis developmental pattern: FoxN1 expression in the thymic primordium inhibits tubulogenesis and induces the expression of genes involved in TEC differentiation, which culminates with the expression of functional cell markers, i.e., MHCII, CD80, Aire in both postnatal Ikaros-/- and WT thymi after arrival of lymphoid progenitor cells.


Assuntos
Células Epiteliais/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Timo/metabolismo , Animais , Diferenciação Celular , Fatores de Transcrição Forkhead/análise , Camundongos , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Morfogênese , Timo/química , Timo/citologia
12.
Nat Commun ; 10(1): 3993, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488837

RESUMO

Planar cell polarity (PCP) plays crucial roles in developmental processes such as gastrulation, neural tube closure and hearing. Wnt pathway mutants are often classified as PCP mutants due to similarities between their phenotypes. Here, we show that in the zebrafish lateral line, disruptions of the PCP and Wnt pathways have differential effects on hair cell orientations. While mutations in the PCP genes vangl2 and scrib cause random orientations of hair cells, mutations in wnt11f1, gpc4 and fzd7a/b induce hair cells to adopt a concentric pattern. This concentric pattern is not caused by defects in PCP but is due to misaligned support cells. The molecular basis of the support cell defect is unknown but we demonstrate that the PCP and Wnt pathways work in parallel to establish proper hair cell orientation. Consequently, hair cell orientation defects are not solely explained by defects in PCP signaling, and some hair cell phenotypes warrant re-evaluation.


Assuntos
Polaridade Celular/genética , Polaridade Celular/fisiologia , Células Ciliadas Auditivas/metabolismo , Via de Sinalização Wnt/genética , Via de Sinalização Wnt/fisiologia , Peixe-Zebra/genética , Animais , Regulação da Expressão Gênica no Desenvolvimento , Proteoglicanas de Heparan Sulfato/genética , Proteínas de Membrana/genética , Morfogênese/genética , Morfogênese/fisiologia , Mutação , Defeitos do Tubo Neural/genética , Neurulação/genética , Receptores de Superfície Celular/genética , Proteína Wnt1/genética , Proteínas de Peixe-Zebra/genética
13.
Nat Commun ; 10(1): 4080, 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501435

RESUMO

Hyphae represent a hallmark structure of multicellular fungi. The evolutionary origins of hyphae and of the underlying genes are, however, hardly known. By systematically analyzing 72 complete genomes, we here show that hyphae evolved early in fungal evolution probably via diverse genetic changes, including co-option and exaptation of ancient eukaryotic (e.g. phagocytosis-related) genes, the origin of new gene families, gene duplications and alterations of gene structure, among others. Contrary to most multicellular lineages, the origin of filamentous fungi did not correlate with expansions of kinases, receptors or adhesive proteins. Co-option was probably the dominant mechanism for recruiting genes for hypha morphogenesis, while gene duplication was apparently less prevalent, except in transcriptional regulators and cell wall - related genes. We identified 414 novel gene families that show correlated evolution with hyphae and that may have contributed to its evolution. Our results suggest that hyphae represent a unique multicellular organization that evolved by limited fungal-specific innovations and gene duplication but pervasive co-option and modification of ancient eukaryotic functions.


Assuntos
Fungos/citologia , Fungos/genética , Genômica , Hifas/citologia , Hifas/genética , Evolução Molecular , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Genes Fúngicos , Morfogênese/genética , Família Multigênica , Fagocitose/genética , Filogenia , Leveduras/genética
14.
Eur. j. anat ; 23(5): 369-376, sept. 2019. ilus, graf, tab
Artigo em Inglês | IBECS | ID: ibc-183867

RESUMO

Hepatic organogenesis is a complex process involving various molecular and cellular determinants. Knowledge of the anatomical and functional structure of the liver and its relationship with other abdominal organs is fundamental from a surgical point of view. Clinical autopsies were performed upon twelve fetal specimens. Photographic footage was reviewed for fetal livers presenting macroscopic abnormalities, and relevant cases were included. A search was conducted employing terms pertaining hepatic malformations’ morphogenetic, anatomical and pathological features. A thorough review was elaborated introducing an updated classification based on autopsy findings and available literature. Twelve fetal specimens underwent clinical autopsies. Gestational age ranged between 18 and 38 weeks (mean 28 weeks). All livers displayed symmetrical lobes. Seven of them presented at least one dysmorphic feature on macroscopic examination. Hepatic malformations can be classified into anomalies due to excessive development, defective development or extrinsic factors. The relevance of the proper identification of liver malformations lies in the broad spectrum of clinical manifestations with different degrees of morbidity associated with them


No disponible


Assuntos
Humanos , Feto/anormalidades , Feto/anatomia & histologia , Fígado/anormalidades , Fígado/anatomia & histologia , Cadáver , Morfogênese , Autopsia/métodos , Fígado/patologia , Organogênese
15.
C R Biol ; 342(5-6): 220-229, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31400945

RESUMO

The in vitro cultivation of date palm staminodes (vestigial stamens) at different stages of female floral ontogenesis confirms the persistence at an immature state of such organs at all the floral differentiation stages. This is evidenced even in fully mature female flowers. Our study revealed the advanced developmental patterns of these rudimentary structures, which bear diverse morphogenetic potentialities. In vitro cultivation of staminodes provides new opportunities for in vitro regeneration of date palm. Such developmental processes were found to be modulated by the stage of floral differentiation, which closely reflected the level of staminode maturity. Development was also impacted by the composition and concentration in plant growth regulators (NAA, BAP and 2,4-D) of the culture media. The large morphogenetic plasticity of the staminodes disposed them to evolutionary variations of the date palm reproduction system. The practical benefits (micropropagation) and the fundamental interests (evolutionary process) of our investigation are discussed.


Assuntos
Evolução Biológica , Phoeniceae/fisiologia , Ácido 2,4-Diclorofenoxiacético/farmacologia , Compostos de Benzil/farmacologia , Meios de Cultura , Flores/crescimento & desenvolvimento , Flores/fisiologia , Herbicidas/farmacologia , Morfogênese , Ácidos Naftalenoacéticos/farmacologia , Reguladores de Crescimento de Planta/farmacologia , Purinas/farmacologia
16.
Mar Drugs ; 17(8)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31409009

RESUMO

Formulas derived from theoretical physics provide important insights about the nematocyst discharge process of Cnidaria (Hydra, jellyfishes, box-jellyfishes and sea-anemones). Our model description of the fastest process in living nature raises and answers questions related to the material properties of the cell- and tubule-walls of nematocysts including their polysialic acid (polySia) dependent target function. Since a number of tumor-cells, especially brain-tumor cells such as neuroblastoma tissues carry the polysaccharide chain polySia in similar concentration as fish eggs or fish skin, it makes sense to use these findings for new diagnostic and therapeutic approaches in the field of nanomedicine. Therefore, the nematocyst discharge process can be considered as a bionic blue-print for future nanomedical devices in cancer diagnostics and therapies. This approach is promising because the physical background of this process can be described in a sufficient way with formulas presented here. Additionally, we discuss biophysical and biochemical experiments which will allow us to define proper boundary conditions in order to support our theoretical model approach. PolySia glycans occur in a similar density on malignant tumor cells than on the cell surfaces of Cnidarian predators and preys. The knowledge of the polySia-dependent initiation of the nematocyst discharge process in an intact nematocyte is an essential prerequisite regarding the further development of target-directed nanomedical devices for diagnostic and therapeutic purposes. The theoretical description as well as the computationally and experimentally derived results about the biophysical and biochemical parameters can contribute to a proper design of anti-tumor drug ejecting vessels which use a stylet-tubule system. Especially, the role of nematogalectins is of interest because these bridging proteins contribute as well as special collagen fibers to the elastic band properties. The basic concepts of the nematocyst discharge process inside the tubule cell walls of nematocysts were studied in jellyfishes and in Hydra which are ideal model organisms. Hydra has already been chosen by Alan Turing in order to figure out how the chemical basis of morphogenesis can be described in a fundamental way. This encouraged us to discuss the action of nematocysts in relation to morphological aspects and material requirements. Using these insights, it is now possible to discuss natural and artificial nematocyst-like vessels with optimized properties for a diagnostic and therapeutic use, e.g., in neurooncology. We show here that crucial physical parameters such as pressure thresholds and elasticity properties during the nematocyst discharge process can be described in a consistent and satisfactory way with an impact on the construction of new nanomedical devices.


Assuntos
Cnidários/química , Ácido N-Acetilneuramínico/química , Nematocisto/química , Animais , Parede Celular/química , Cubomedusas/química , Elasticidade/efeitos dos fármacos , Humanos , Hydra/química , Morfogênese/efeitos dos fármacos , Nanomedicina/métodos
17.
Nat Commun ; 10(1): 3465, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31371714

RESUMO

Brain morphogenesis is an important process contributing to higher-order cognition, however our knowledge about its biological basis is largely incomplete. Here we analyze 118 neuroanatomical parameters in 1,566 mutant mouse lines and identify 198 genes whose disruptions yield NeuroAnatomical Phenotypes (NAPs), mostly affecting structures implicated in brain connectivity. Groups of functionally similar NAP genes participate in pathways involving the cytoskeleton, the cell cycle and the synapse, display distinct fetal and postnatal brain expression dynamics and importantly, their disruption can yield convergent phenotypic patterns. 17% of human unique orthologues of mouse NAP genes are known loci for cognitive dysfunction. The remaining 83% constitute a vast pool of genes newly implicated in brain architecture, providing the largest study of mouse NAP genes and pathways. This offers a complementary resource to human genetic studies and predict that many more genes could be involved in mammalian brain morphogenesis.


Assuntos
Encéfalo , Estudos de Associação Genética , Morfogênese/genética , Neuroanatomia , Neurogênese/genética , Animais , Encéfalo/metabolismo , Ciclo Celular , Cognição , Citoesqueleto , Redes Reguladoras de Genes , Genes Letais/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Mutação , Fenótipo , Sinapses
18.
Nat Cell Biol ; 21(8): 966-977, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31371827

RESUMO

Migrasomes are recently identified vesicular organelles that form on retraction fibres behind migrating cells. Whether migrasomes are present in vivo and, if so, the function of migrasomes in living organisms is unknown. Here, we show that migrasomes are formed during zebrafish gastrulation and signalling molecules, such as chemokines, are enriched in migrasomes. We further demonstrate that Tspan4 and Tspan7 are required for migrasome formation. Organ morphogenesis is impaired in zebrafish MZtspan4a and MZtspan7 mutants. Mechanistically, migrasomes are enriched on a cavity underneath the embryonic shield where they serve as chemoattractants to ensure the correct positioning of dorsal forerunner cells vegetally next to the embryonic shield, thereby affecting organ morphogenesis. Our study shows that migrasomes are signalling organelles that provide specific biochemical information to coordinate organ morphogenesis.


Assuntos
Embrião não Mamífero/metabolismo , Morfogênese/fisiologia , Organelas/metabolismo , Proteínas de Peixe-Zebra/genética , Animais , Padronização Corporal/fisiologia , Movimento Celular/genética , Movimento Celular/fisiologia , Desenvolvimento Embrionário/fisiologia , Gastrulação/fisiologia , Organelas/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Peixe-Zebra/embriologia
19.
Eur Phys J E Soft Matter ; 42(8): 104, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31418095

RESUMO

Current knowledge on limbs development lacks a physical description of the forces leading to formation of the limbs precursors or "buds". Earlier stages of development are driven by large scale morphogenetic movements, such as dipolar vortical flows and mechanical buckling, pulled by rings of cells. It is a natural hypothesis that similar phenomena occur during limb formation. However it is difficult to experiment on the developmental forces, in such a complex dynamic system. Here, we report a physical study of hindlimb bud formation in the chicken embryo. We use electrical stimulation to enhance the physical forces present in the tissue, prior to limb bud formation. By triggering the physical forces in a rapid and amplified pattern, we reveal the mechanism of formation of the hindlimbs: the early presumptive embryonic territory is composed of a set of rings encased like Russian dolls. Each ring constricts in an excitable pattern of force, and the limb buds are generated by folding at a pre-existing boundary between two rings, forming the dorsal and ventral ectoderms. The amniotic sac buckles at another boundary. Physiologically, the actuator of the excitable force is the tail bud pushing posteriorly along the median axis. The developmental dynamics suggests how animals may evolve by modification of the magnitude of these forces, within a common broken symmetry. On a practical level, localized electrical stimulation of morphogenetic forces opens the way to in vivo electrical engineering of tissues.


Assuntos
Botões de Extremidades/embriologia , Morfogênese , Animais , Embrião de Galinha , Elasticidade , Estimulação Elétrica , Viscosidade
20.
Insect Biochem Mol Biol ; 112: 103206, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31425850

RESUMO

Wings are an indispensable structure in many insects for their foraging, courtship, escape from predators, and migration. Cuticular proteins are major components of the insect cuticle and wings, but there is limited information on how cuticular proteins may play an essential role in wing morphogenesis. We identified a wing-specific cuticular protein, LmACP7, which belongs to the RR-2 subfamily of CPR chitin-binding proteins in the migratory locust. LmACP7 was initially produced in epidermal cells and subsequently migrated to the exocuticle at the pre-ecdysial stage in adult wings. Depletion of LmACP7 transcripts by RNA interference markedly reduced its protein amounts, which consequently led to abnormal wing morphogenesis. The deformed wings were curved, wrinkled, and failed to fully expand. We further demonstrated that the deformation was caused by both severe damage of the endocuticle and death of the epidermal cells in the wings. Based on these data, we propose that LmACP7 not only serves as an essential structural protein in the wing but is also required for the integrity of wing epithelial cells. LmACP7 contributes to production of the wing endocuticle and to the morphogenesis of functional wings in the migratory locust.


Assuntos
Proteínas de Insetos/genética , Locusta migratoria/genética , Asas de Animais/crescimento & desenvolvimento , Animais , Quitina/metabolismo , Células Epidérmicas/metabolismo , Proteínas de Insetos/metabolismo , Locusta migratoria/crescimento & desenvolvimento , Metamorfose Biológica/genética , Morfogênese/genética , Ninfa/genética , Ninfa/crescimento & desenvolvimento , Interferência de RNA , Asas de Animais/anormalidades
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