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1.
Methods Mol Biol ; 2364: 199-216, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34542855

RESUMO

Spermatogenesis is one of the most dramatic cellular differentiation events observed in animals. In particular, spermiogenesis (the final stage of spermatogenesis) involves extensive shedding of cytoplasmic organelles, dramatic nuclear rearrangements, and assembly of long flagellar structures. In planarian flatworms, the spherical nucleus present in round spermatids elongates to produce the filamentous nucleus of mature sperm. Newly formed cortical microtubules participate in cytoskeletal rearrangements observed during spermiogenesis and remain present in sperm. In addition, a pair of flagella assemble at one end of each spermatid in a process that likely involves de novo formation of centrioles. This chapter includes a brief introduction to planarian spermatogenesis and current tools for the analysis of molecular players in this process. Step-by-step protocols for isolating and imaging spermatogenic cells are provided with enough detail to be carried out by newcomers to the field who would like to study this unique organism in the laboratory.


Assuntos
Planárias , Animais , Núcleo Celular , Masculino , Microtúbulos , Morfogênese , Espermátides , Espermatogênese , Espermatozoides
2.
Methods Mol Biol ; 2303: 645-653, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34626413

RESUMO

The primary left and right bronchial buds grow and sprout secondary bronchi, which in turn develop tertiary bronchi, and so on. Branching continues for a total of 6-8 generations in the mouse and for about 23 generations in humans, forming the estimated 50 million branches of the human lung. Thus, patterns of branching are incalculably complex. However, these branches are rarely random, implying that they are under genetic control. Genomic information alone cannot specify the patterning information in terms of where the branching occurs and the direction it grows as well as their size and shape. There is a complex choreography among glycosaminoglycans and growth factors/morphogens that provide a highly complex instructive cues that control lung branching and development of the functional lung. Herein, we describe the use of xylosides in the manipulation of glycosaminoglycan (GAG) biosynthesis and study the effect of xyloside-primed GAGs in the regulation of lung branching events.


Assuntos
Pulmão , Animais , Glicosaminoglicanos , Glicosídeos , Camundongos , Morfogênese , Técnicas de Cultura de Tecidos
3.
Heart Fail Clin ; 18(1): 139-153, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34776075

RESUMO

The genetic background of congenital heart diseases (CHDs) is extremely complex, heterogenous, and still majorly to be determined. CHDs can be sporadic or familial. In this article we discuss in detail the phenotypic spectrum of selected genes including MYH7, GATA4, NKX2-5, TBX5, and TBX20. Our goal is to offer the clinician a general overview of the clinical spectrum of the analyzed topics that are traditionally known as causative for CHDs but we underline in this review the possible progressive functional (cardiomyopathy) and electric aspects (arrhythmias) caused by the genetic background.


Assuntos
Cardiomiopatias , Cardiopatias Congênitas , Fator de Transcrição GATA4 , Cardiopatias Congênitas/genética , Humanos , Morfogênese/genética , Miocárdio
4.
Cell ; 184(26): 6313-6325.e18, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34942099

RESUMO

How tissues acquire complex shapes is a fundamental question in biology and regenerative medicine. Zebrafish semicircular canals form from invaginations in the otic epithelium (buds) that extend and fuse to form the hubs of each canal. We find that conventional actomyosin-driven behaviors are not required. Instead, local secretion of hyaluronan, made by the enzymes uridine 5'-diphosphate dehydrogenase (ugdh) and hyaluronan synthase 3 (has3), drives canal morphogenesis. Charged hyaluronate polymers osmotically swell with water and generate isotropic extracellular pressure to deform the overlying epithelium into buds. The mechanical anisotropy needed to shape buds into tubes is conferred by a polarized distribution of actomyosin and E-cadherin-rich membrane tethers, which we term cytocinches. Most work on tissue morphogenesis ascribes actomyosin contractility as the driving force, while the extracellular matrix shapes tissues through differential stiffness. Our work inverts this expectation. Hyaluronate pressure shaped by anisotropic tissue stiffness may be a widespread mechanism for powering morphological change in organogenesis and tissue engineering.


Assuntos
Espaço Extracelular/química , Ácido Hialurônico/farmacologia , Morfogênese , Especificidade de Órgãos , Pressão , Canais Semicirculares/citologia , Canais Semicirculares/embriologia , Actomiosina/metabolismo , Animais , Anisotropia , Comportamento Animal , Matriz Extracelular/metabolismo , Ácido Hialurônico/biossíntese , Modelos Biológicos , Morfogênese/efeitos dos fármacos , Especificidade de Órgãos/efeitos dos fármacos , Pressão Osmótica , Canais Semicirculares/diagnóstico por imagem , Comportamento Estereotipado , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/metabolismo
5.
Philos Trans A Math Phys Eng Sci ; 379(2213): 20200274, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34743596

RESUMO

Skin patterns are the first example of the existence of Turing patterns in living organisms. Extensive research on zebrafish, a model organism with stripes on its skin, has revealed the principles of pattern formation at the molecular and cellular levels. Surprisingly, although the networks of cell-cell interactions have been observed to satisfy the 'short-range activation and long-range inhibition' prerequisites for Turing pattern formation, numerous individual reactions were not envisioned based on the classical reaction-diffusion model. For example, in real skin, it is not an alteration in concentrations of chemicals, but autonomous migration and proliferation of pigment cells that establish patterns, and cell-cell interactions are mediated via direct contact through cell protrusions. Therefore, the classical reaction-diffusion mechanism cannot be used as it is for modelling skin pattern formation. Various studies are underway to adapt mathematical models to the experimental findings on research into skin patterns, and the purpose of this review is to organize and present them. These novel theoretical methods could be applied to autonomous pattern formation phenomena other than skin patterns. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.


Assuntos
Modelos Biológicos , Peixe-Zebra , Animais , Difusão , Morfogênese , Pele
6.
Philos Trans A Math Phys Eng Sci ; 379(2213): 20200273, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34743597

RESUMO

Virtually all forms of life, from single-cell eukaryotes to complex, highly differentiated multicellular organisms, exhibit a property referred to as symmetry. However, precise measures of symmetry are often difficult to formulate and apply in a meaningful way to biological systems, where symmetries and asymmetries can be dynamic and transient, or be visually apparent but not reliably quantifiable using standard measures from mathematics and physics. Here, we present and illustrate a novel measure that draws on concepts from information theory to quantify the degree of symmetry, enabling the identification of approximate symmetries that may be present in a pattern or a biological image. We apply the measure to rotation, reflection and translation symmetries in patterns produced by a Turing model, as well as natural objects (algae, flowers and leaves). This method of symmetry quantification is unbiased and rigorous, and requires minimal manual processing compared to alternative measures. The proposed method is therefore a useful tool for comparison and identification of symmetries in biological systems, with potential future applications to symmetries that arise during development, as observed in vivo or as produced by mathematical models. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.


Assuntos
Modelos Teóricos , Física , Matemática , Modelos Biológicos , Morfogênese , Plantas
7.
Philos Trans A Math Phys Eng Sci ; 379(2213): 20200272, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34743598

RESUMO

Turing patterns have morphed from mathematical curiosities into highly desirable targets for synthetic biology. For a long time, their biological significance was sometimes disputed but there is now ample evidence for their involvement in processes ranging from skin pigmentation to digit and limb formation. While their role in developmental biology is now firmly established, their synthetic design has so far proved challenging. Here, we review recent large-scale mathematical analyses that have attempted to narrow down potential design principles. We consider different aspects of robustness of these models and outline why this perspective will be helpful in the search for synthetic Turing-patterning systems. We conclude by considering robustness in the context of developmental modelling more generally. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.


Assuntos
Modelos Biológicos , Biologia Sintética , Morfogênese
8.
Philos Trans A Math Phys Eng Sci ; 379(2213): 20200278, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34743599

RESUMO

Turing patterns are commonly understood as specific instabilities of a spatially homogeneous steady state, resulting from activator-inhibitor interaction destabilized by diffusion. We argue that this view is restrictive and its agreement with biological observations is problematic. We present two alternatives to the classical Turing analysis of patterns. First, we employ the abstract framework of evolution equations to enable the study of far-from-equilibrium patterns. Second, we introduce a mechano-chemical model, with the surface on which the pattern forms being dynamic and playing an active role in the pattern formation, effectively replacing the inhibitor. We highlight the advantages of these two alternatives vis-à-vis the classical Turing analysis, and give an overview of recent results and future challenges for both approaches. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.


Assuntos
Modelos Biológicos , Modelos Químicos , Difusão , Retroalimentação , Morfogênese
9.
Philos Trans A Math Phys Eng Sci ; 379(2213): 20200276, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34743601

RESUMO

Some analytical and numerical results are presented for pattern formation properties associated with novel types of reaction-diffusion (RD) systems that involve the coupling of bulk diffusion in the interior of a multi-dimensional spatial domain to nonlinear processes that occur either on the domain boundary or within localized compartments that are confined within the domain. The class of bulk-membrane system considered herein is derived from an asymptotic analysis in the limit of small thickness of a thin domain that surrounds the bulk medium. When the bulk domain is a two-dimensional disk, a weakly nonlinear analysis is used to characterize Turing and Hopf bifurcations that can arise from the linearization around a radially symmetric, but spatially non-uniform, steady-state of the bulk-membrane system. In a singularly perturbed limit, the existence and linear stability of localized membrane-bound spike patterns is analysed for a Gierer-Meinhardt activator-inhibitor model that includes bulk coupling. Finally, the emergence of collective intracellular oscillations is studied for a class of PDE-ODE bulk-cell model in a bounded two-dimensional domain that contains spatially localized, but dynamically active, circular cells that are coupled through a linear bulk diffusion field. Applications of such coupled bulk-membrane or bulk-cell systems to some biological systems are outlined, and some open problems in this area are discussed. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.


Assuntos
Modelos Biológicos , Difusão , Morfogênese
10.
Philos Trans A Math Phys Eng Sci ; 379(2213): 20200269, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34743602

RESUMO

In 1952, Alan Turing proposed a theory showing how morphogenesis could occur from a simple two morphogen reaction-diffusion system [Turing, A. M. (1952) Phil. Trans. R. Soc. Lond. A 237, 37-72. (doi:10.1098/rstb.1952.0012)]. While the model is simple, it has found diverse applications in fields such as biology, ecology, behavioural science, mathematics and chemistry. Chemistry in particular has made significant contributions to the study of Turing-type morphogenesis, providing multiple reproducible experimental methods to both predict and study new behaviours and dynamics generated in reaction-diffusion systems. In this review, we highlight the historical role chemistry has played in the study of the Turing mechanism, summarize the numerous insights chemical systems have yielded into both the dynamics and the morphological behaviour of Turing patterns, and suggest future directions for chemical studies into Turing-type morphogenesis. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.


Assuntos
Modelos Biológicos , Difusão , Morfogênese
11.
Philos Trans A Math Phys Eng Sci ; 379(2213): 20200268, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34743603

RESUMO

In the nearly seven decades since the publication of Alan Turing's work on morphogenesis, enormous progress has been made in understanding both the mathematical and biological aspects of his proposed reaction-diffusion theory. Some of these developments were nascent in Turing's paper, and others have been due to new insights from modern mathematical techniques, advances in numerical simulations and extensive biological experiments. Despite such progress, there are still important gaps between theory and experiment, with many examples of biological patterning where the underlying mechanisms are still unclear. Here, we review modern developments in the mathematical theory pioneered by Turing, showing how his approach has been generalized to a range of settings beyond the classical two-species reaction-diffusion framework, including evolving and complex manifolds, systems heterogeneous in space and time, and more general reaction-transport equations. While substantial progress has been made in understanding these more complicated models, there are many remaining challenges that we highlight throughout. We focus on the mathematical theory, and in particular linear stability analysis of 'trivial' base states. We emphasize important open questions in developing this theory further, and discuss obstacles in using these techniques to understand biological reality. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.


Assuntos
Modelos Biológicos , Difusão , Matemática , Morfogênese
12.
Philos Trans A Math Phys Eng Sci ; 379(2213): 20200270, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34743605

RESUMO

Periodic patterns form intricate arrays in the vertebrate anatomy, notably the hair and feather follicles of the skin, but also internally the villi of the gut and the many branches of the lung, kidney, mammary and salivary glands. These tissues are composite structures, being composed of adjoined epithelium and mesenchyme, and the patterns that arise within them require interaction between these two tissue layers. In embryonic development, cells change both their distribution and state in a periodic manner, defining the size and relative positions of these specialized structures. Their placement is determined by simple spacing mechanisms, with substantial evidence pointing to a variety of local enhancement/lateral inhibition systems underlying the breaking of symmetry. The nature of the cellular processes involved, however, has been less clear. While much attention has focused on intercellular soluble signals, such as protein growth factors, experimental evidence has grown for contributions of cell movement or mechanical forces to symmetry breaking. In the mesenchyme, unlike the epithelium, cells may move freely and can self-organize into aggregates by chemotaxis, or through generation and response to mechanical strain on their surrounding matrix. Different modes of self-organization may coexist, either coordinated into a single system or with hierarchical relationships. Consideration of a broad range of distinct biological processes is required to advance understanding of biological pattern formation. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.


Assuntos
Modelos Biológicos , Pele , Animais , Morfogênese , Vertebrados
13.
Philos Trans A Math Phys Eng Sci ; 379(2213): 20200280, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34743606

RESUMO

Elucidating pattern forming processes is an important problem in the physical, chemical and biological sciences. Turing's contribution, after being initially neglected, eventually catalysed a huge amount of work from mathematicians, physicists, chemists and biologists aimed towards understanding how steady spatial patterns can emerge from homogeneous chemical mixtures due to the reaction and diffusion of different chemical species. While this theory has been developed mathematically and investigated experimentally for over half a century, many questions still remain unresolved. This theme issue places Turing's theory of pattern formation in a modern context, discussing the current frontiers in foundational aspects of pattern formation in reaction-diffusion and related systems. It highlights ongoing work in chemical, synthetic and developmental settings which is helping to elucidate how important Turing's mechanism is for real morphogenesis, while highlighting gaps that remain in matching theory to reality. The theme issue also surveys a variety of recent mathematical research pushing the boundaries of Turing's original theory to more realistic and complicated settings, as well as discussing open theoretical challenges in the analysis of such models. It aims to consolidate current research frontiers and highlight some of the most promising future directions. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.


Assuntos
Modelos Biológicos , Difusão , Matemática , Morfogênese
14.
J Math Biol ; 83(5): 55, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34727234

RESUMO

In this paper we consider mathematical modeling of the dynamics of self-organized patterning of spatially confined human embryonic stem cells (hESCs) treated with BMP4 (gastruloids) described in recent experimental works (Warmflash in Nat Methods 11:847-854, 2014; Chhabra in PloS Biol 17: 3000498, 2019). In the first part of the paper we use the activator-inhibitor equations of Gierer and Meinhardt to identify 3 reaction-diffusion regimes for each of the three morphogenic proteins, BMP4, Wnt and Nodal, based on the characteristic features of the dynamic patterning. We identify appropriate boundary conditions which correspond to the experimental setup and perform numerical simulations of the reaction-diffusion (RD) systems, using the finite element approximation, to confirm that the RD systems in these regimes produce realistic dynamics of the protein concentrations. In the second part of the paper we use analytic tools to address the questions of the existence and stability of non-homogeneous steady states for the reaction-diffusion systems of the type considered in the first part of the paper.


Assuntos
Células-Tronco Embrionárias Humanas , Difusão , Humanos , Modelos Biológicos , Morfogênese
15.
Elife ; 102021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609280

RESUMO

During morphogenesis, epithelial sheets remodel into complex geometries. How cells dynamically organise their contact with neighbouring cells in these tightly packed tissues is poorly understood. We have used light-sheet microscopy of growing mouse embryonic lung explants, three-dimensional cell segmentation, and physical theory to unravel the principles behind 3D cell organisation in growing pseudostratified epithelia. We find that cells have highly irregular 3D shapes and exhibit numerous neighbour intercalations along the apical-basal axis as well as over time. Despite the fluidic nature, the cell packing configurations follow fundamental relationships previously described for apical epithelial layers, that is, Euler's polyhedron formula, Lewis' law, and Aboav-Weaire's law, at all times and across the entire tissue thickness. This arrangement minimises the lateral cell-cell surface energy for a given cross-sectional area variability, generated primarily by the distribution and movement of nuclei. We conclude that the complex 3D cell organisation in growing epithelia emerges from simple physical principles.


Assuntos
Pulmão/embriologia , Animais , Células Epiteliais/citologia , Epitélio/embriologia , Camundongos , Morfogênese
16.
BMC Plant Biol ; 21(1): 448, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615467

RESUMO

BACKGROUND: Cotton is an important cash crop. The fiber length has always been a hot spot, but multi-factor control of fiber quality makes it complex to understand its genetic basis. Previous reports suggested that OsGASR9 promotes germination, width, and thickness by GAs in rice, while the overexpression of AtGASA10 leads to reduced silique length, which is likely to reduce cell wall expansion. Therefore, this study aimed to explore the function of GhGASA10 in cotton fibers development. RESULTS: To explore the molecular mechanisms underlying fiber elongation regulation concerning GhGASA10-1, we revealed an evolutionary basis, gene structure, and expression. Our results emphasized the conservative nature of GASA family with its origin in lower fern plants S. moellendorffii. GhGASA10-1 was localized in the cell membrane, which may synthesize and transport secreted proteins to the cell wall. Besides, GhGASA10-1 promoted seedling germination and root extension in transgenic Arabidopsis, indicating that GhGASA10-1 promotes cell elongation. Interestingly, GhGASA10-1 was upregulated by IAA at fiber elongation stages. CONCLUSION: We propose that GhGASA10-1 may promote fiber elongation by regulating the synthesis of cellulose induced by IAA, to lay the foundation for future research on the regulation networks of GASA10-1 in cotton fiber development.


Assuntos
Proliferação de Células/genética , Gossypium/crescimento & desenvolvimento , Gossypium/genética , Ácidos Indolacéticos/metabolismo , Morfogênese/efeitos dos fármacos , Morfogênese/genética , Reguladores de Crescimento de Plantas/metabolismo , Proliferação de Células/efeitos dos fármacos , Fibra de Algodão , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo
17.
Phys Rev Lett ; 127(13): 138102, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34623834

RESUMO

Because the normal operation of the eye depends on sensitive morphogenetic processes for its eventual shape, developmental flaws can lead to wide-ranging ocular defects. However, the physical processes and mechanisms governing ocular morphogenesis are not well understood. Here, using analytical theory and nonlinear shell finite-element simulations, we show, for optic vesicles experiencing matrix-constrained growth, that elastic instabilities govern the optic cup morphogenesis. By capturing the stress amplification owing to mass increase during growth, we show that the morphogenesis is driven by two elastic instabilities analogous to the snap through in spherical shells, where the second instability is sensitive to the optic cup geometry. In particular, if the optic vesicle is too slender, it will buckle and break axisymmetry, thus, preventing normal development. Our results shed light on the morphogenetic mechanisms governing the formation of a functional biological system and the role of elastic instabilities in the shape selection of soft biological structures.


Assuntos
Olho/crescimento & desenvolvimento , Modelos Biológicos , Fenômenos Biofísicos , Morfogênese , Disco Óptico/crescimento & desenvolvimento
18.
Nat Commun ; 12(1): 6019, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650052

RESUMO

During morphogenesis, molecular mechanisms that orchestrate biomechanical dynamics across cells remain unclear. Here, we show a role of guidance receptor Plexin-B2 in organizing actomyosin network and adhesion complexes during multicellular development of human embryonic stem cells and neuroprogenitor cells. Plexin-B2 manipulations affect actomyosin contractility, leading to changes in cell stiffness and cytoskeletal tension, as well as cell-cell and cell-matrix adhesion. We have delineated the functional domains of Plexin-B2, RAP1/2 effectors, and the signaling association with ERK1/2, calcium activation, and YAP mechanosensor, thus providing a mechanistic link between Plexin-B2-mediated cytoskeletal tension and stem cell physiology. Plexin-B2-deficient stem cells exhibit premature lineage commitment, and a balanced level of Plexin-B2 activity is critical for maintaining cytoarchitectural integrity of the developing neuroepithelium, as modeled in cerebral organoids. Our studies thus establish a significant function of Plexin-B2 in orchestrating cytoskeletal tension and cell-cell/cell-matrix adhesion, therefore solidifying the importance of collective cell mechanics in governing stem cell physiology and tissue morphogenesis.


Assuntos
Actomiosina/metabolismo , Adesão Celular/fisiologia , Citoesqueleto/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco/metabolismo , Actinas , Sistemas CRISPR-Cas , Diferenciação Celular , Junções Célula-Matriz/metabolismo , Células-Tronco Embrionárias , Edição de Genes , Expressão Gênica , Humanos , Mecanotransdução Celular , Morfogênese , Células-Tronco Neurais , Semaforinas , Transdução de Sinais
19.
Int J Mol Sci ; 22(19)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34638598

RESUMO

Apoptosis, or programmed cell death, is a form of cell suicide that is extremely important for ridding the body of cells that are no longer required, to protect the body against hazardous cells, such as cancerous ones, and to promote tissue morphogenesis during animal development. Upon reception of a death stimulus, the doomed cell activates biochemical pathways that eventually converge on the activation of dedicated enzymes, caspases. Numerous pieces of information on the biochemical control of the process have been gathered, from the successive events of caspase activation to the identification of their targets, such as lamins, which constitute the nuclear skeleton. Yet, evidence from multiple systems now shows that apoptosis is also a mechanical process, which may even ultimately impinge on the morphogenesis of the surrounding tissues. This mechanical role relies on dramatic actomyosin cytoskeleton remodelling, and on its coupling with the nucleus before nucleus fragmentation. Here, we provide an overview of apoptosis before describing how apoptotic forces could combine with selective caspase-dependent proteolysis to orchestrate nucleus destruction.


Assuntos
Apoptose/fisiologia , Núcleo Celular/metabolismo , Actomiosina/metabolismo , Animais , Caspases/metabolismo , Morte Celular/fisiologia , Citoesqueleto/metabolismo , Humanos , Morfogênese/fisiologia
20.
Curr Top Membr ; 87: 131-151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34696883

RESUMO

Living cells are exposed to multiple mechanical stimuli from the extracellular matrix or from surrounding cells. Mechanoreceptors are molecules that display status changes in response to mechanical stimulation, transforming physical cues into biological responses to help the cells adapt to dynamic changes of the microenvironment. Mechanical stimuli are responsible for shaping the tridimensional development and patterning of the organs in early embryonic stages. The development of the heart is one of the first morphogenetic events that occur in embryos. As the circulation is established, the vascular system is exposed to constant shear stress, which is the force created by the movement of blood. Both spatial and temporal variations in shear stress differentially modulate critical steps in heart development, such as trabeculation and compaction of the ventricular wall and the formation of the heart valves. Zebrafish embryos are small, transparent, have a short developmental period and allow for real-time visualization of a variety of fluorescently labeled proteins to recapitulate developmental dynamics. In this review, we will highlight the application of zebrafish models as a genetically tractable model for investigating cardiovascular development and regeneration. We will introduce our approaches to manipulate mechanical forces during critical stages of zebrafish heart development and in a model of vascular regeneration, as well as advances in imaging technologies to capture these processes at high resolution. Finally, we will discuss the role of molecules of the Plexin family and Piezo cation channels as major mechanosensors recently implicated in cardiac morphogenesis.


Assuntos
Mecanotransdução Celular , Peixe-Zebra , Animais , Modelos Animais , Morfogênese , Estresse Mecânico
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