-
The EMBO Journal Nov 2023The establishment and maintenance of apical-basal polarity is a fundamental step in brain development, instructing the organization of neural progenitor cells (NPCs) and...
The establishment and maintenance of apical-basal polarity is a fundamental step in brain development, instructing the organization of neural progenitor cells (NPCs) and the developing cerebral cortex. Particularly, basally located extracellular matrix (ECM) is crucial for this process. In vitro, epithelial polarization can be achieved via endogenous ECM production, or exogenous ECM supplementation. While neuroepithelial development is recapitulated in neural organoids, the effects of different ECM sources in tissue morphogenesis remain underexplored. Here, we show that exposure to a solubilized basement membrane matrix substrate, Matrigel, at early neuroepithelial stages causes rapid tissue polarization and rearrangement of neuroepithelial architecture. In cultures exposed to pure ECM components or unexposed to any exogenous ECM, polarity acquisition is slower and driven by endogenous ECM production. After the onset of neurogenesis, tissue architecture and neuronal differentiation are largely independent of the initial ECM source, but Matrigel exposure has long-lasting effects on tissue patterning. These results advance the knowledge on mechanisms of exogenously and endogenously guided morphogenesis, demonstrating the self-sustainability of neuroepithelial cultures by endogenous processes.
Topics: Humans; Extracellular Matrix; Morphogenesis; Organoids
PubMed: 37842725
DOI: 10.15252/embj.2022113213 -
Current Osteoporosis Reports Dec 2023Here, we discuss the origin of chondrocytes, their destiny, and their plasticity in relationship to bone growth, articulation, and formation of the trabeculae. We also... (Review)
Review
PURPOSE OF REVIEW
Here, we discuss the origin of chondrocytes, their destiny, and their plasticity in relationship to bone growth, articulation, and formation of the trabeculae. We also consider these processes from a biological, clinical, and evolutionary perspective.
RECENT FINDINGS
Chondrocytes, which provide the template for the formation of most bones, are responsible for skeletal growth and articulation during postnatal life. In recent years our understanding of the fate of these cells has changed dramatically. Current evidence indicates a paradoxical situation during skeletogenesis, with some cells of mesenchymal condensation differentiating directly into osteoblasts, whereas others of the same kind give rise to highly similar osteoblasts via a complex process of differentiation involving several chondrocyte intermediates. The situation becomes even more paradoxical during postnatal growth when stem cells in the growth plate produce differentiated, functional progenies, which thereafter presumably dedifferentiate into another type of stem cell. Such a remarkable transition from one cell type to another under postnatal physiological conditions provides a fascinating example of cellular plasticity that may have valuable clinical implications.
Topics: Humans; Chondrocytes; Cell Plasticity; Osteogenesis; Bone Development; Bone and Bones; Osteoblasts; Growth Plate; Cell Differentiation
PubMed: 37837512
DOI: 10.1007/s11914-023-00827-1 -
Science Advances Aug 2023Organoids are a major new tool to study tissue renewal. However, characterizing the underlying differentiation dynamics remains challenging. Here, we developed...
Organoids are a major new tool to study tissue renewal. However, characterizing the underlying differentiation dynamics remains challenging. Here, we developed TypeTracker, which identifies cell fates by AI-enabled cell tracking and propagating end point fates back along the branched lineage trees. Cells that ultimately migrate to the villus commit to their new type early, when still deep inside the crypt, with important consequences: (i) Secretory cells commit before terminal division, with secretory fates emerging symmetrically in sister cells. (ii) Different secretory types descend from distinct stem cell lineages rather than an omnipotent secretory progenitor. (iii) The ratio between secretory and absorptive cells is strongly affected by proliferation after commitment. (iv) Spatial patterning occurs after commitment through type-dependent cell rearrangements. This "commit-then-sort" model contrasts with the conventional conveyor belt picture, where cells differentiate by moving up the crypt-villus axis and hence raises new questions about the underlying commitment and sorting mechanisms.
Topics: Cell Differentiation; Organoids; Cell Lineage; Biological Transport; Cell Movement
PubMed: 37595032
DOI: 10.1126/sciadv.add6480 -
The Journal of Cell Biology Nov 2023Astrocytes control the formation of specific synaptic circuits via cell adhesion and secreted molecules. Astrocyte synaptogenic functions are dependent on the...
Astrocytes control the formation of specific synaptic circuits via cell adhesion and secreted molecules. Astrocyte synaptogenic functions are dependent on the establishment of their complex morphology. However, it is unknown if distinct neuronal cues differentially regulate astrocyte morphogenesis. δ-Catenin was previously thought to be a neuron-specific protein that regulates dendrite morphology. We found δ-catenin is also highly expressed by astrocytes and required both in astrocytes and neurons for astrocyte morphogenesis. δ-Catenin is hypothesized to mediate transcellular interactions through the cadherin family of cell adhesion proteins. We used structural modeling and biochemical analyses to reveal that δ-catenin interacts with the N-cadherin juxtamembrane domain to promote N-cadherin surface expression. An autism-linked δ-catenin point mutation impaired N-cadherin cell surface expression and reduced astrocyte complexity. In the developing mouse cortex, only lower-layer cortical neurons express N-cadherin. Remarkably, when we silenced astrocytic N-cadherin throughout the cortex, only lower-layer astrocyte morphology was disrupted. These findings show that δ-catenin controls astrocyte-neuron cadherin interactions that regulate layer-specific astrocyte morphogenesis.
Topics: Animals; Mice; Astrocytes; Cadherins; Delta Catenin; Morphogenesis; Neurons
PubMed: 37707499
DOI: 10.1083/jcb.202303138 -
Angiogenesis Nov 2023Following the process of vasculogenesis during development, angiogenesis generates new vascular structures through a variety of different mechanisms or modes. These...
Following the process of vasculogenesis during development, angiogenesis generates new vascular structures through a variety of different mechanisms or modes. These different modes of angiogenesis involve, for example, increasing microvasculature density by sprouting of endothelial cells, splitting of vessels to increase vascular surface area by intussusceptive angiogenesis, fusion of capillaries to increase blood flow by coalescent angiogenesis, and the recruitment of non-endothelial cells by vasculogenic mimicry. The recent reporting on coalescent angiogenesis as a new mode of vessel formation warrants a brief overview of angiogenesis mechanisms to provide a more complete picture. The journal Angiogenesis is devoted to the delineation of the different modes and mechanisms that collectively dictate blood vessel formation, inhibition, and function in health and disease.
Topics: Neovascularization, Physiologic; Endothelial Cells; Capillaries; Morphogenesis
PubMed: 37640982
DOI: 10.1007/s10456-023-09895-4 -
ELife Nov 2023In vitro culture systems that structurally model human myogenesis and promote PAX7 myogenic progenitor maturation have not been established. Here we report that human...
In vitro culture systems that structurally model human myogenesis and promote PAX7 myogenic progenitor maturation have not been established. Here we report that human skeletal muscle organoids can be differentiated from induced pluripotent stem cell lines to contain paraxial mesoderm and neuromesodermal progenitors and develop into organized structures reassembling neural plate border and dermomyotome. Culture conditions instigate neural lineage arrest and promote fetal hypaxial myogenesis toward limb axial anatomical identity, with generation of sustainable uncommitted PAX7 myogenic progenitors and fibroadipogenic (PDGFRa+) progenitor populations equivalent to those from the second trimester of human gestation. Single-cell comparison to human fetal and adult myogenic progenitor /satellite cells reveals distinct molecular signatures for non-dividing myogenic progenitors in activated (//) and dormant (//) states. Our approach provides a robust 3D in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis.
Topics: Humans; Muscle, Skeletal; Cell Differentiation; Fetus; Satellite Cells, Skeletal Muscle; Muscle Development; PAX7 Transcription Factor
PubMed: 37963071
DOI: 10.7554/eLife.87081 -
Frontiers in Immunology 2023
Topics: Lymphocytes; Immunity, Innate; Cytokines; Cell Lineage
PubMed: 38077316
DOI: 10.3389/fimmu.2023.1338463 -
Nature Communications Sep 2023Serotonin is a neurotransmitter that signals through 5-HT receptors to control key functions in the nervous system. Serotonin receptors are also ubiquitously expressed...
Serotonin is a neurotransmitter that signals through 5-HT receptors to control key functions in the nervous system. Serotonin receptors are also ubiquitously expressed in various organs and have been detected in embryos of different organisms. Potential morphogenetic functions of serotonin signaling have been proposed based on pharmacological studies but a mechanistic understanding is still lacking. Here, we uncover a role of serotonin signaling in axis extension of Drosophila embryos by regulating Myosin II (MyoII) activation, cell contractility and cell intercalation. We find that serotonin and serotonin receptors 5HT2A and 5HT2B form a signaling module that quantitatively regulates the amplitude of planar polarized MyoII contractility specified by Toll receptors and the GPCR Cirl. Remarkably, serotonin signaling also regulates actomyosin contractility at cell junctions, cellular flows and epiblast morphogenesis during chicken gastrulation. This phylogenetically conserved mechanical function of serotonin signaling in regulating actomyosin contractility and tissue flow reveals an ancestral role in morphogenesis of multicellular organisms.
Topics: Animals; Serotonin; Actomyosin; Actin Cytoskeleton; Signal Transduction; Cytoskeletal Proteins; Drosophila; Morphogenesis
PubMed: 37684231
DOI: 10.1038/s41467-023-41178-w -
The Journal of Cell Biology Dec 2023Although mutations in the SCRIB gene lead to multiple morphological organ defects in vertebrates, the molecular pathway linking SCRIB to organ shape anomalies remains...
Although mutations in the SCRIB gene lead to multiple morphological organ defects in vertebrates, the molecular pathway linking SCRIB to organ shape anomalies remains elusive. Here, we study the impact of SCRIB-targeted gene mutations during the formation of the gut epithelium in an organ-on-chip model. We show that SCRIB KO gut-like epithelia are flatter with reduced exposed surface area. Cell differentiation on filters further shows that SCRIB plays a critical role in the control of apical cell shape, as well as in the basoapical polarization of myosin light chain localization and activity. Finally, we show that SCRIB serves as a molecular scaffold for SHROOM2/4 and ROCK1 and identify an evolutionary conserved SHROOM binding site in the SCRIB carboxy-terminal that is required for SCRIB function in the control of apical cell shape. Our results demonstrate that SCRIB plays a key role in epithelial morphogenesis by controlling the epithelial apical contractility during cell differentiation.
Topics: Animals; Binding Sites; Biological Evolution; Cell Differentiation; Cell Shape; Epithelium; Microphysiological Systems; Membrane Proteins; Morphogenesis
PubMed: 37930352
DOI: 10.1083/jcb.202211113 -
Current Opinion in Genetics &... Dec 2023How functional organisms arise from a single cell is a fundamental question in biology with direct relevance to understanding developmental defects and diseases.... (Review)
Review
How functional organisms arise from a single cell is a fundamental question in biology with direct relevance to understanding developmental defects and diseases. Dissecting developmental processes provides the basic, critical framework for understanding disease progression and treatment. Bottom-up approaches to recapitulate formation of various components of the embryo have been effective to probe symmetry-breaking, self-organisation, tissue patterning and morphogenesis. However, these studies have been mostly concerned with axial patterning, which is essentially longitudinal. Can these models generate the appendicular axes? If so, how far can self-organisation take these? Will experimentally induced organisers be required? This short review explores these questions, highlighting how minimal models are essential for understanding patterning and morphogenetic processes.
Topics: Body Patterning; Morphogenesis; Embryo, Mammalian
PubMed: 37897953
DOI: 10.1016/j.gde.2023.102130