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Development (Cambridge, England) Jan 2020The tooth provides an excellent system for deciphering the molecular mechanisms of organogenesis, and has thus been of longstanding interest to developmental and stem... (Review)
Review
The tooth provides an excellent system for deciphering the molecular mechanisms of organogenesis, and has thus been of longstanding interest to developmental and stem cell biologists studying embryonic morphogenesis and adult tissue renewal. In recent years, analyses of molecular signaling networks, together with new insights into cellular heterogeneity, have greatly improved our knowledge of the dynamic epithelial-mesenchymal interactions that take place during tooth development and homeostasis. Here, we review recent progress in the field of mammalian tooth morphogenesis and also discuss the mechanisms regulating stem cell-based dental tissue homeostasis, regeneration and repair. These exciting findings help to lay a foundation that will ultimately enable the application of fundamental research discoveries toward therapies to improve oral health.
Topics: Animals; Homeostasis; Humans; Morphogenesis; Odontogenesis; Regeneration; Signal Transduction; Tooth
PubMed: 31980484
DOI: 10.1242/dev.184754 -
Nature Biomedical Engineering Apr 2022Human spinal-cord-like tissues induced from human pluripotent stem cells are typically insufficiently mature and do not mimic the morphological features of neurulation....
Human spinal-cord-like tissues induced from human pluripotent stem cells are typically insufficiently mature and do not mimic the morphological features of neurulation. Here, we report a three-dimensional culture system and protocol for the production of human spinal-cord-like organoids (hSCOs) recapitulating the neurulation-like tube-forming morphogenesis of the early spinal cord. The hSCOs exhibited neurulation-like tube-forming morphogenesis, cellular differentiation into the major types of spinal-cord neurons as well as glial cells, and mature synaptic functional activities, among other features of the development of the spinal cord. We used the hSCOs to screen for antiepileptic drugs that can cause neural-tube defects. hSCOs may also facilitate the study of the development of the human spinal cord and the modelling of diseases associated with neural-tube defects.
Topics: Humans; Morphogenesis; Neural Tube Defects; Neurulation; Organoids; Spinal Cord
PubMed: 35347276
DOI: 10.1038/s41551-022-00868-4 -
Current Opinion in Cell Biology Dec 2021Organoids are three-dimensional structures that self-organize from human pluripotent stem cells or primary tissue, potentially serving as a traceable and manipulatable... (Review)
Review
Organoids are three-dimensional structures that self-organize from human pluripotent stem cells or primary tissue, potentially serving as a traceable and manipulatable platform to facilitate our understanding of organogenesis. Despite the ongoing advancement in generating organoids of diverse systems, biological applications of in vitro generated organoids remain as a major challenge in part due to a substantial lack of intricate complexity. The studies of development and regeneration enumerate the essential roles of highly diversified nonepithelial populations such as mesenchyme and endothelium in directing fate specification, morphogenesis, and maturation. Furthermore, organoids with physiological and homeostatic functions require direct and indirect inter-organ crosstalk recapitulating what is seen in organogenesis. We herein review the evolving organoid technology at the cell, tissue, organ, and system level with a main emphasis on endoderm derivatives.
Topics: Endoderm; Humans; Morphogenesis; Organogenesis; Organoids; Pluripotent Stem Cells
PubMed: 34352726
DOI: 10.1016/j.ceb.2021.06.007 -
Nature Cell Biology Aug 2019Migrasomes are recently identified vesicular organelles that form on retraction fibres behind migrating cells. Whether migrasomes are present in vivo and, if so, the...
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.
Topics: Animals; Body Patterning; Cell Movement; Embryo, Nonmammalian; Embryonic Development; Gastrulation; Morphogenesis; Organelles; Signal Transduction; Zebrafish; Zebrafish Proteins
PubMed: 31371827
DOI: 10.1038/s41556-019-0358-6 -
Current Opinion in Cell Biology Feb 2021Mechanical forces generated by living cells at the molecular level propagate to the cellular and organismal level and have profound consequences for embryogenesis. A... (Review)
Review
Mechanical forces generated by living cells at the molecular level propagate to the cellular and organismal level and have profound consequences for embryogenesis. A direct result of force application is movement, as occurs in chromosome separation, cell migration, or tissue folding. A less direct, but equally important effect of force, is the activation of mechanosensitive signaling, which allows cells to probe their mechanical surrounding and communicate with each other over short and long distances. In this review, we focus on forces as a means of conveying information and affecting cell behavior during embryogenesis. We discuss four developmental processes that demonstrate the involvement of force in cell fate determination, growth, morphogenesis, and organogenesis, in a variety of model organisms. Finally, a generalizable pathway of mechanosensing and mechanotransduction in vivo is described, and we highlight similarities between morphogens and forces in patterning of embryos.
Topics: Animals; Cell Differentiation; Cell Movement; Cell Physiological Phenomena; Embryonic Development; Gastrulation; Humans; Mechanotransduction, Cellular; Morphogenesis; Organogenesis; Protein Conformation; Transcription, Genetic
PubMed: 32898827
DOI: 10.1016/j.ceb.2020.08.007 -
Cell Feb 2023Axial development of mammals involves coordinated morphogenetic events, including axial elongation, somitogenesis, and neural tube formation. To gain insight into the...
Axial development of mammals involves coordinated morphogenetic events, including axial elongation, somitogenesis, and neural tube formation. To gain insight into the signals controlling the dynamics of human axial morphogenesis, we generated axially elongating organoids by inducing anteroposterior symmetry breaking of spatially coupled epithelial cysts derived from human pluripotent stem cells. Each organoid was composed of a neural tube flanked by presomitic mesoderm sequentially segmented into somites. Periodic activation of the somite differentiation gene MESP2 coincided in space and time with anteriorly traveling segmentation clock waves in the presomitic mesoderm of the organoids, recapitulating critical aspects of somitogenesis. Timed perturbations demonstrated that FGF and WNT signaling play distinct roles in axial elongation and somitogenesis, and that FGF signaling gradients drive segmentation clock waves. By generating and perturbing organoids that robustly recapitulate the architecture of multiple axial tissues in human embryos, this work offers a means to dissect mechanisms underlying human embryogenesis.
Topics: Animals; Humans; Body Patterning; Embryonic Development; Gene Expression Regulation, Developmental; Mammals; Mesoderm; Morphogenesis; Somites; Wnt Signaling Pathway; Organoids
PubMed: 36657441
DOI: 10.1016/j.cell.2022.12.042 -
Seminars in Cell & Developmental Biology Sep 2023The process by which biological systems such as cells, tissues and organisms acquire shape has been named as morphogenesis and it is central to a plethora of biological... (Review)
Review
The process by which biological systems such as cells, tissues and organisms acquire shape has been named as morphogenesis and it is central to a plethora of biological contexts including embryo development, wound healing, or even cancer. Morphogenesis relies in both self-organising properties of the system and in environmental inputs (biochemical and biophysical). The classical view of morphogenesis is based on the study of external biochemical molecules, such as morphogens. However, recent studies are establishing that the mechanical environment is also used by cells to communicate within tissues, suggesting that this mechanical crosstalk is essential to synchronise morphogenetic transitions and self-organisation. In this article we discuss how tissue interaction drive robust morphogenesis, starting from a classical biochemical view, to finalise with more recent advances on how the biophysical properties of a tissue feedback with their surroundings to allow form acquisition. We also comment on how in silico models aid to integrate and predict changes in cell and tissue behaviour. Finally, considering recent advances from the developmental biomechanics field showing that mechanical inputs work as cues that promote morphogenesis, we invite to revisit the concept of morphogen.
Topics: Morphogenesis; Embryonic Development; Biomechanical Phenomena; Signal Transduction; Models, Biological
PubMed: 37002130
DOI: 10.1016/j.semcdb.2023.03.010 -
Developmental Cell Jan 2021Mechanical forces are integral to development-from the earliest stages of embryogenesis to the construction and differentiation of complex organs. Advances in imaging... (Review)
Review
Mechanical forces are integral to development-from the earliest stages of embryogenesis to the construction and differentiation of complex organs. Advances in imaging and biophysical tools have allowed us to delve into the developmental mechanobiology of increasingly complex organs and organisms. Here, we focus on recent work that highlights the diversity and importance of mechanical influences during morphogenesis. Developing tissues experience intrinsic mechanical signals from active forces and changes to tissue mechanical properties as well as extrinsic mechanical signals, including constraint and compression, pressure, and shear forces. Finally, we suggest promising avenues for future work in this rapidly expanding field.
Topics: Animals; Biomechanical Phenomena; Biophysics; Cell Differentiation; Embryonic Development; Humans; Mechanotransduction, Cellular; Morphogenesis; Signal Transduction
PubMed: 33321105
DOI: 10.1016/j.devcel.2020.11.025 -
Current Topics in Developmental Biology 2020Tunicates are a diverse group of invertebrate marine chordates that includes the larvaceans, thaliaceans, and ascidians. Because of their unique evolutionary position as... (Review)
Review
Tunicates are a diverse group of invertebrate marine chordates that includes the larvaceans, thaliaceans, and ascidians. Because of their unique evolutionary position as the sister group of the vertebrates, tunicates are invaluable as a comparative model and hold the promise of revealing both conserved and derived features of chordate gastrulation. Descriptive studies in a broad range of tunicates have revealed several important unifying traits that make them unique among the chordates, including invariant cell lineages through gastrula stages and an overall morphological simplicity. Gastrulation has only been studied in detail in ascidians such as Ciona and Phallusia, where it involves a simple cup-shaped gastrula driven primarily by endoderm invagination. This appears to differ significantly from vertebrate models, such as Xenopus, in which mesoderm convergent extension and epidermal epiboly are major contributors to involution. These differences may reflect the cellular simplicity of the ascidian embryo.
Topics: Animals; Body Patterning; Cell Lineage; Embryo, Nonmammalian; Endoderm; Evolution, Molecular; Gastrula; Gastrulation; Gene Expression Regulation, Developmental; Morphogenesis; Urochordata
PubMed: 31959289
DOI: 10.1016/bs.ctdb.2019.09.001 -
Development (Cambridge, England) Aug 2022The gut has been a central subject of organogenesis since Caspar Friedrich Wolff's seminal 1769 work 'De Formatione Intestinorum'. Today, we are moving from a purely... (Review)
Review
The gut has been a central subject of organogenesis since Caspar Friedrich Wolff's seminal 1769 work 'De Formatione Intestinorum'. Today, we are moving from a purely genetic understanding of cell specification to a model in which genetics codes for layers of physical-mechanical and electrical properties that drive organogenesis such that organ function and morphogenesis are deeply intertwined. This Review provides an up-to-date survey of the extrinsic and intrinsic mechanical forces acting on the embryonic vertebrate gut during development and of their role in all aspects of intestinal morphogenesis: enteric nervous system formation, epithelium structuring, muscle orientation and differentiation, anisotropic growth and the development of myogenic and neurogenic motility. I outline numerous implications of this biomechanical perspective in the etiology and treatment of pathologies, such as short bowel syndrome, dysmotility, interstitial cells of Cajal-related disorders and Hirschsprung disease.
Topics: Cell Differentiation; Enteric Nervous System; Hirschsprung Disease; Humans; Morphogenesis; Organogenesis
PubMed: 35980364
DOI: 10.1242/dev.200765