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Nature Communications Apr 2023The outgrowth of epithelial bud followed by reiterated bifurcations during renal development is driven by the ligand-receptor interactions between the epithelium and the...
The outgrowth of epithelial bud followed by reiterated bifurcations during renal development is driven by the ligand-receptor interactions between the epithelium and the surrounding mesenchyme. Here, by exploring ligand-receptor interactions in E10.5 and E11.5 kidneys by single cell RNA-seq, we find that Isthmin1 (Ism1), a secreted protein, resembles Gdnf expression and modulates kidney branching morphogenesis. Mice deficient for Ism1 exhibit defective ureteric bud bifurcation and impaired metanephric mesenchyme condensation in E11.5 embryos, attributable to the compromised Gdnf/Ret signaling, ultimately leading to renal agenesis and hypoplasia/dysplasia. By HRP-induced proximity labelling, we further identify integrin α8β1 as a receptor of Ism1 in E11.5 kidney and demonstrate that Ism1 promoted cell-cell adhesion through interacting with Integrin α8β1, the receptor whose activation is responsible for Gdnf expression and mesenchyme condensation. Taken together, our work reveals Ism1 as a critical regulator of cell-cell interaction that modulates Gdnf/Ret signaling during early kidney development.
Topics: Mice; Animals; Glial Cell Line-Derived Neurotrophic Factor; Proto-Oncogene Proteins c-ret; Ligands; Kidney; Morphogenesis; Mesoderm; Intercellular Signaling Peptides and Proteins
PubMed: 37185772
DOI: 10.1038/s41467-023-37992-x -
Cellular and Molecular Life Sciences :... Feb 2021During embryogenesis, the processes that control how cells differentiate and interact to form particular tissues and organs with precise timing and shape are of... (Review)
Review
During embryogenesis, the processes that control how cells differentiate and interact to form particular tissues and organs with precise timing and shape are of fundamental importance. One prominent example of such processes is vertebrate somitogenesis, which is governed by a molecular oscillator called the segmentation clock. The segmentation clock system is initiated in the presomitic mesoderm in which a set of genes and signaling pathways exhibit coordinated spatiotemporal dynamics to establish regularly spaced boundaries along the body axis; these boundaries provide a blueprint for the development of segment-like structures such as spines and skeletal muscles. The highly complex and dynamic nature of this in vivo event and the design principles and their regulation in both normal and abnormal embryogenesis are not fully understood. Recently, live-imaging has been used to quantitatively analyze the dynamics of selected components of the circuit, particularly in combination with well-designed experiments to perturb the system. Here, we review recent progress from studies using live imaging and manipulation, including attempts to recapitulate the segmentation clock in vitro. In combination with mathematical modeling, these techniques have become essential for disclosing novel aspects of the clock.
Topics: Biological Clocks; Body Patterning; Cell Differentiation; Embryonic Development; Gene Expression Regulation, Developmental; Humans; Mesoderm; Models, Theoretical; Signal Transduction; Somites
PubMed: 33015720
DOI: 10.1007/s00018-020-03655-z -
International Journal of Molecular... Nov 2021The simplification of alveoli leads to various lung pathologies such as bronchopulmonary dysplasia and emphysema. Deep insight into the process of emergence of the... (Review)
Review
The simplification of alveoli leads to various lung pathologies such as bronchopulmonary dysplasia and emphysema. Deep insight into the process of emergence of the secondary septa during development and regeneration after pneumonectomy, and into the contribution of the drivers of alveologenesis and neo-alveolarization is required in an efficient search for therapeutic approaches. In this review, we describe the formation of the gas exchange units of the lung as a multifactorial process, which includes changes in the actomyosin cytoskeleton of alveocytes and myofibroblasts, elastogenesis, retinoic acid signaling, and the contribution of alveolar mesenchymal cells in secondary septation. Knowledge of the mechanistic context of alveologenesis remains incomplete. The characterization of the mechanisms that govern the emergence and depletion of αSMA will allow for an understanding of how the niche of fibroblasts is changing. Taking into account the intense studies that have been performed on the pool of lung mesenchymal cells, we present data on the typing of interstitial fibroblasts and their role in the formation and maintenance of alveoli. On the whole, when identifying cell subpopulations in lung mesenchyme, one has to consider the developmental context, the changing cellular functions, and the lability of gene signatures.
Topics: Actomyosin; Bronchopulmonary Dysplasia; Cell Lineage; Cytoskeleton; Emphysema; Gases; Humans; Lung; Mesoderm; Myofibroblasts; Organogenesis; Pulmonary Alveoli; Tretinoin
PubMed: 34829987
DOI: 10.3390/ijms222212107 -
Cells & Development Sep 2021Early in animal development many cells are conditionally specified based on observations that those cells can be directed toward alternate fates. The endomesoderm is so... (Review)
Review
Early in animal development many cells are conditionally specified based on observations that those cells can be directed toward alternate fates. The endomesoderm is so named because early specification produces cells that often have been observed to simultaneously express both early endoderm and mesoderm transcription factors. Experiments with these cells demonstrate that their progeny can directed entirely toward endoderm or mesoderm, whereas normally they establish both germ layers. This review examines the mechanisms that initiate the conditional endomesoderm state, its metastability, and the mechanisms that resolve that state into definitive endoderm and mesoderm.
Topics: Animals; Body Patterning; Endoderm; Humans; Mesoderm; Models, Biological; Sea Urchins; Signal Transduction
PubMed: 34245941
DOI: 10.1016/j.cdev.2021.203716 -
Development (Cambridge, England) Nov 2023Tissue interactions are essential for guiding organ development and regeneration. Hair follicle formation relies on inductive signalling between two tissues, the...
Tissue interactions are essential for guiding organ development and regeneration. Hair follicle formation relies on inductive signalling between two tissues, the embryonic surface epithelium and the adjacent mesenchyme. Although previous research has highlighted the hair-inducing potential of the mesenchymal component of the hair follicle - the dermal papilla and its precursor, the dermal condensate - the source and nature of the primary inductive signal before dermal condensate formation have remained elusive. Here, we performed epithelial-mesenchymal tissue recombination experiments using hair-forming back skin and glabrous plantar skin from mouse embryos to unveil that the back skin mesenchyme is inductive even before dermal condensate formation. Moreover, the naïve, unpatterned mesenchyme was sufficient to trigger hair follicle formation even in the oral epithelium. Building on previous knowledge, we explored the hair-inductive ability of the Wnt agonist R-spondin 1 and a Bmp receptor inhibitor in embryonic skin explants. Although R-spondin 1 instigated precocious placode-specific transcriptional responses, it was insufficient for hair follicle induction, either alone or in combination with Bmp receptor inhibition. Our findings pave the way for identifying the hair follicle-inducing cue.
Topics: Mice; Animals; Hair Follicle; Hair; Skin; Mesoderm; Bone Morphogenetic Protein Receptors
PubMed: 37982496
DOI: 10.1242/dev.202140 -
Current Topics in Developmental Biology 2020In birds as in all amniotes, the site of gastrulation is a midline structure, the primitive streak. This appears as cells in the one cell-thick epiblast undergo... (Review)
Review
In birds as in all amniotes, the site of gastrulation is a midline structure, the primitive streak. This appears as cells in the one cell-thick epiblast undergo epithelial-to-mesenchymal transition to ingress and form definitive mesoderm and endoderm. Global movements involving tens of thousands of cells in the embryonic epiblast precede gastrulation. They position the primitive streak precursors from a marginal position (equivalent to the situation in anamniotes) along the future antero-posterior axis (typical for amniotes). These epithelial movements continue in modified form during gastrulation, when they are accompanied by collective movements of different class in the forming mesoderm and endoderm. Here I discuss the nature of these collective cell movements shaping the embryo, their interplay with signaling events controlling fate specification and significance in an evolutionary perspective.
Topics: Animals; Cell Movement; Chick Embryo; Chickens; Endoderm; Gastrula; Gastrulation; Gene Expression Regulation, Developmental; Mesoderm; Signal Transduction; Zebrafish Proteins; Zygote
PubMed: 31959297
DOI: 10.1016/bs.ctdb.2019.11.015 -
Current Topics in Developmental Biology 2024For almost a century, developmental biologists have appreciated that the ability of the embryonic organizer to induce and pattern the body plan is intertwined with its... (Review)
Review
For almost a century, developmental biologists have appreciated that the ability of the embryonic organizer to induce and pattern the body plan is intertwined with its differentiation into axial mesoderm. Despite this, we still have a relatively poor understanding of the contribution of axial mesoderm to induction and patterning of different body regions, and the manner in which axial mesoderm-derived information is interpreted in tissues of changing competence. Here, with a particular focus on the nervous system, we review the evidence that axial mesoderm notochord and prechordal mesoderm/mesendoderm act as organizers, discuss how their influence extends through the different axes of the developing organism, and describe how the ability of axial mesoderm to direct morphogenesis impacts on its role as a local organizer.
Topics: Mesoderm; Morphogenesis; Nervous System; Body Patterning; Brain; Face; Germ Layers
PubMed: 38556460
DOI: 10.1016/bs.ctdb.2024.02.007 -
Advances in Experimental Medicine and... 2024The development of the inflow tract is undoubtedly one of the most complex remodeling events in the formation of the four-chambered heart. It involves the creation of...
The development of the inflow tract is undoubtedly one of the most complex remodeling events in the formation of the four-chambered heart. It involves the creation of two separate atrial chambers, the formation of an atrial/atrioventricular (AV) septal complex, the incorporation of the caval veins and coronary sinus into the right atrium, and the remodeling events that result in pulmonary venous return draining into the left atrium. In these processes, the atrioventricular mesenchymal complex, consisting of the major atrioventricular (AV) cushions, the mesenchymal cap on the primary atrial septum (pAS), and the dorsal mesenchymal protrusion (DMP), plays a crucial role.
Topics: Animals; Humans; Coronary Sinus; Heart; Heart Atria; Mesoderm; Pulmonary Veins
PubMed: 38884709
DOI: 10.1007/978-3-031-44087-8_7 -
Nature Reviews. Molecular Cell Biology Jul 2024Segmentation is a fundamental feature of the vertebrate body plan. This metameric organization is first implemented by somitogenesis in the early embryo, when paired... (Review)
Review
Segmentation is a fundamental feature of the vertebrate body plan. This metameric organization is first implemented by somitogenesis in the early embryo, when paired epithelial blocks called somites are rhythmically formed to flank the neural tube. Recent advances in in vitro models have offered new opportunities to elucidate the mechanisms that underlie somitogenesis. Notably, models derived from human pluripotent stem cells introduced an efficient proxy for studying this process during human development. In this Review, we summarize the current understanding of somitogenesis gained from both in vivo studies and in vitro studies. We deconstruct the spatiotemporal dynamics of somitogenesis into four distinct modules: dynamic events in the presomitic mesoderm, segmental determination, somite anteroposterior polarity patterning, and epithelial morphogenesis. We first focus on the segmentation clock, as well as signalling and metabolic gradients along the tissue, before discussing the clock and wavefront and other models that account for segmental determination. We then detail the molecular and cellular mechanisms of anteroposterior polarity patterning and somite epithelialization.
Topics: Somites; Animals; Humans; Body Patterning; Vertebrates; Gene Expression Regulation, Developmental; Embryonic Development; Mesoderm; Signal Transduction; Morphogenesis
PubMed: 38418851
DOI: 10.1038/s41580-024-00709-z -
Cells & Development Dec 2021Early in animal development many cells are conditionally specified based on observations that those cells can be directed toward alternate fates. The endomesoderm is so... (Review)
Review
Early in animal development many cells are conditionally specified based on observations that those cells can be directed toward alternate fates. The endomesoderm is so named because early specification produces cells that often have been observed to simultaneously express both early endoderm and mesoderm transcription factors. Experiments with these cells demonstrate that their progeny can directed entirely toward endoderm or mesoderm, whereas normally they establish both germ layers. This review examines the mechanisms that initiate the conditional endomesoderm state, its metastability, and the mechanisms that resolve that state into definitive endoderm and mesoderm.
Topics: Animals; Embryo, Nonmammalian; Endoderm; Mesoderm; Sea Urchins; Signal Transduction
PubMed: 34610899
DOI: 10.1016/j.cdev.2021.203731