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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 Opinion in Cell Biology Dec 2023Biophysical signaling organizes forces to drive tissue morphogenesis, a process co-opted during disease progression. The systematic buildup of forces at the tissue scale... (Review)
Review
Biophysical signaling organizes forces to drive tissue morphogenesis, a process co-opted during disease progression. The systematic buildup of forces at the tissue scale is energetically demanding. Just as mechanical forces, gene expression, and concentrations of morphogens vary spatially across a developing tissue, there might similarly be spatial variations in energy consumption. Recent studies have started to uncover the connections between spatial patterns of mechanical forces and spatial patterns of energy metabolism. Here, we define and review the concept of energy metabolism during tissue morphogenesis. We highlight experiments showing spatial variations in energy metabolism across several model systems, categorized by morphogenetic motif, including convergent extension, branching, and migration. Finally, we discuss approaches to further enable quantitative measurements of energy production and consumption during morphogenesis.
Topics: Morphogenesis; Signal Transduction; Energy Metabolism
PubMed: 37696131
DOI: 10.1016/j.ceb.2023.102235 -
Physical Biology Sep 2023Understanding the collective physical processes that drive robust morphological transitions in animal development necessitates the characterization of the relevant...
Understanding the collective physical processes that drive robust morphological transitions in animal development necessitates the characterization of the relevant fields involved in morphogenesis. Calcium (Ca) is recognized as one such field. In this study, we demonstrate that the spatial fluctuations of Caduringregeneration exhibit universal characteristics. To investigate this phenomenon, we employ two distinct controls, an external electric field and, a gap junction-blocking drug. Both lead to the modulation of the Caactivity and a reversible halting of the regeneration process. The application of an electric field enhances Caactivity in the's tissue and increases its spatial correlations, while the administration ofinhibits its activity and diminishes the spatial correlations. Remarkably, the statistical characteristics of Caspatial fluctuations, including the coefficient of variation and skewness, manifest universal shape distributions across tissue samples and conditions. We introduce a field-theoretic model, describing fluctuations in a tilted double-well potential, which successfully captures these universal properties. Moreover, our analysis reveals that the Caactivity is spatially localized, and the's tissue operates near the onset of bistability, where the local Caactivity fluctuates between low and high excited states in distinct regions. These findings highlight the prominent role of the Cafield inmorphogenesis and provide insights into the underlying mechanisms governing robust morphological transitions.
Topics: Animals; Calcium; Morphogenesis
PubMed: 37696269
DOI: 10.1088/1478-3975/acf8a4 -
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 -
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 -
Plant Physiology Aug 2023Cell polarity is intimately linked to numerous biological processes, such as oriented plant cell division, particular asymmetric division, cell differentiation, cell and... (Review)
Review
Cell polarity is intimately linked to numerous biological processes, such as oriented plant cell division, particular asymmetric division, cell differentiation, cell and tissue morphogenesis, and transport of hormones and nutrients. Cell polarity is typically initiated by a polarizing cue that regulates the spatiotemporal dynamic of polarity molecules, leading to the establishment and maintenance of polar domains at the plasma membrane. Despite considerable progress in identifying key polarity regulators in plants, the molecular and cellular mechanisms underlying cell polarity formation have yet to be fully elucidated. Recent work suggests a critical role for membrane protein/lipid nanodomains in polarized morphogenesis in plants. One outstanding question is how the spatiotemporal dynamics of signaling nanodomains are controlled to achieve robust cell polarization. In this review, we first summarize the current state of knowledge on potential regulatory mechanisms of nanodomain dynamics, with a special focus on Rho-like GTPases from plants. We then discuss the pavement cell system as an example of how cells may integrate multiple signals and nanodomain-involved feedback mechanisms to achieve robust polarity. A mechanistic understanding of nanodomains' roles in plant cell polarity is still in the early stages and will remain an exciting area for future investigations.
Topics: Signal Transduction; Plants; Cell Membrane; Membranes; Morphogenesis; Cell Polarity
PubMed: 37194569
DOI: 10.1093/plphys/kiad288 -
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 -
Biochimica Et Biophysica Acta. General... Aug 2023Cancer invasion and metastasis accounts for the majority of cancer related mortality. A better understanding of the players that drive the aberrant invasion and... (Review)
Review
Cancer invasion and metastasis accounts for the majority of cancer related mortality. A better understanding of the players that drive the aberrant invasion and migration of tumors cells will provide critical targets to inhibit metastasis. Postnatal pubertal mammary gland morphogenesis is characterized by highly proliferative, invasive, and migratory normal epithelial cells. Identifying the molecular regulators of pubertal gland development is a promising strategy since tumorigenesis and metastasis is postulated to be a consequence of aberrant reactivation of developmental stages. In this review, we summarize the pubertal morphogenesis regulators that are involved in cancer metastasis and revisit pubertal mammary gland transcriptome profiling to uncover both known and unknown metastasis genes. Our updated list of pubertal morphogenesis regulators shows that most are implicated in invasion and metastasis. This review highlights molecular linkages between development and metastasis and provides a guide for exploring novel metastatic drivers.
Topics: Mice; Humans; Animals; Mammary Glands, Human; Gene Expression Profiling; Morphogenesis; Epithelial Cells; Cell Transformation, Neoplastic
PubMed: 37150225
DOI: 10.1016/j.bbagen.2023.130375