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Current Topics in Developmental Biology 2024The anterior-to-posterior (head-to-tail) body axis is extraordinarily diverse among vertebrates but conserved within species. Body axis development requires a population... (Review)
Review
The anterior-to-posterior (head-to-tail) body axis is extraordinarily diverse among vertebrates but conserved within species. Body axis development requires a population of axial progenitors that resides at the posterior of the embryo to sustain elongation and is then eliminated once axis extension is complete. These progenitors occupy distinct domains in the posterior (tail-end) of the embryo and contribute to various lineages along the body axis. The subset of axial progenitors with neuromesodermal competency will generate both the neural tube (the precursor of the spinal cord), and the trunk and tail somites (producing the musculoskeleton) during embryo development. These axial progenitors are called Neuromesodermal Competent cells (NMCs) and Neuromesodermal Progenitors (NMPs). NMCs/NMPs have recently attracted interest beyond the field of developmental biology due to their clinical potential. In the mouse, the maintenance of neuromesodermal competency relies on a fine balance between a trio of known signals: Wnt/β-catenin, FGF signalling activity and suppression of retinoic acid signalling. These signals regulate the relative expression levels of the mesodermal transcription factor Brachyury and the neural transcription factor Sox2, permitting the maintenance of progenitor identity when co-expressed, and either mesoderm or neural lineage commitment when the balance is tilted towards either Brachyury or Sox2, respectively. Despite important advances in understanding key genes and cellular behaviours involved in these fate decisions, how the balance between mesodermal and neural fates is achieved remains largely unknown. In this chapter, we provide an overview of signalling and gene regulatory networks in NMCs/NMPs. We discuss mutant phenotypes associated with axial defects, hinting at the potential significant role of lesser studied proteins in the maintenance and differentiation of the progenitors that fuel axial elongation.
Topics: Animals; Body Patterning; Mesoderm; Gene Expression Regulation, Developmental; Humans; Signal Transduction; T-Box Domain Proteins; Cell Differentiation; Head
PubMed: 38729677
DOI: 10.1016/bs.ctdb.2024.02.012 -
Developmental Dynamics : An Official... May 2023Mammalian calvarium is composed of flat bones developed from two origins, neural crest, and mesoderm. Cells from both origins exhibit similar behavior but express...
BACKGROUND
Mammalian calvarium is composed of flat bones developed from two origins, neural crest, and mesoderm. Cells from both origins exhibit similar behavior but express distinct transcriptomes. It is intriguing to ask whether genes shared by both origins play similar or distinct roles in development. In the present study, we have examined the role of Pdgfra, which is expressed in both neural crest and mesoderm, in specific lineages during calvarial development.
RESULTS
We found that in calvarial progenitor cells, Pdgfra is needed to maintain normal proliferation and migration of neural crest cells but only proliferation of mesoderm cells. Later in calvarial osteoblasts, we found that Pdgfra is necessary for both proliferation and differentiation of neural crest-derived cells, but not for differentiation of mesoderm-derived cells. We also examined the potential interaction between Pdgfra and other signaling pathway involved in calvarial osteoblasts but did not identify significant alteration of Wnt or Hh signaling activity in Pdgfra genetic models.
CONCLUSIONS
Pdgfra is required for normal calvarial development in both neural crest cells and mesoderm cells, but these lineages exhibit distinct responses to alteration of Pdgfra activity.
Topics: Animals; Cell Differentiation; Skull; Receptor Protein-Tyrosine Kinases; Signal Transduction; Neural Crest; Mesoderm; Mammals
PubMed: 36606407
DOI: 10.1002/dvdy.564 -
Journal of Biomedical Science Jun 2022The molecular mechanisms that regulate embryogenesis and cardiac development are calibrated by multiple signal transduction pathways within or between different cell... (Review)
Review
The molecular mechanisms that regulate embryogenesis and cardiac development are calibrated by multiple signal transduction pathways within or between different cell lineages via autocrine or paracrine mechanisms of action. The heart is the first functional organ to form during development, which highlights the importance of this organ in later stages of growth. Knowledge of the regulatory mechanisms underlying cardiac development and adult cardiac homeostasis paves the way for discovering therapeutic possibilities for cardiac disease treatment. Serum response factor (SRF) is a major transcription factor that controls both embryonic and adult cardiac development. SRF expression is needed through the duration of development, from the first mesodermal cell in a developing embryo to the last cell damaged by infarction in the myocardium. Precise regulation of SRF expression is critical for mesoderm formation and cardiac crescent formation in the embryo, and altered SRF levels lead to cardiomyopathies in the adult heart, suggesting the vital role played by SRF in cardiac development and disease. This review provides a detailed overview of SRF and its partners in their various functions and discusses the future scope and possible therapeutic potential of SRF in the cardiovascular system.
Topics: Gene Expression Regulation, Developmental; Heart; Mesoderm; Myocardium; Serum Response Factor; Transcription Factors
PubMed: 35681202
DOI: 10.1186/s12929-022-00820-3 -
Anatomical Science International Mar 2020The musculoskeletal system comprises muscles, tendons, ligaments, and bones. The connection site between muscle and tendon is termed "myotendinous junction," while the... (Review)
Review
The musculoskeletal system comprises muscles, tendons, ligaments, and bones. The connection site between muscle and tendon is termed "myotendinous junction," while the junction between tendon/ligament and bone is termed "enthesis." These two regions are the center of physical function, but how this functional complex is formed during development is unclear. In this review, we discussed recent findings about the development of tissues constituting the musculoskeletal system and the interactions among these tissues during development. The musculoskeletal system of the head develops in the mid-embryonic stage. In addition, head mesoderm-derived cells (muscle anlagen) and cranial neural crest cells (tendon and bone anlagen) interact with each other. Myogenesis initiates in the head without difficulty, even in the absence of cranial neural crest cells; however, muscle tissue does not grow under these conditions and remains small. Tendons, which differentiate from cranial neural crest cells, form myotendinous junctions at the stage at which desmin accumulates in the tendon-side muscle stump, leading to morphological maturation. Therefore, individual tissues (i.e., muscles, tendons, ligaments, and bones) constituting the musculoskeletal system form a functionally important complex, while mutually influencing one another.
Topics: Bone and Bones; Head; Humans; Ligaments; Mesoderm; Muscles; Musculoskeletal Development; Musculoskeletal System; Neural Crest; Tendons
PubMed: 31916224
DOI: 10.1007/s12565-019-00523-0 -
Developmental Cell Jun 2023Oscillator systems achieve synchronization when oscillators are coupled. The presomitic mesoderm is a system of cellular oscillators, where coordinated genetic activity...
Oscillator systems achieve synchronization when oscillators are coupled. The presomitic mesoderm is a system of cellular oscillators, where coordinated genetic activity is necessary for proper periodic generation of somites. While Notch signaling is required for the synchronization of these cells, it is unclear what information the cells exchange and how they react to this information to align their oscillatory pace with that of their neighbors. Combining mathematical modeling and experimental data, we found that interaction between murine presomitic mesoderm cells is controlled by a phase-gated and unidirectional coupling mechanism and results in deceleration of their oscillation pace upon Notch signaling. This mechanism predicts that isolated populations of well-mixed cells synchronize, revealing a stereotypical synchronization in the mouse PSM and contradicting expectations from previously applied theoretical approaches. Collectively, our theoretical and experimental findings reveal the underlying coupling mechanisms of the presomitic mesoderm cells and provide a framework to quantitatively characterize their synchronization.
Topics: Mice; Animals; Biological Clocks; Somites; Mesoderm; Models, Theoretical; Signal Transduction; Gene Expression Regulation, Developmental; Receptors, Notch
PubMed: 37098349
DOI: 10.1016/j.devcel.2023.04.002 -
Development (Cambridge, England) May 2023Cardiac lineage specification in the mouse is controlled by TGFβ and WNT signaling. From fly to fish, BMP has been identified as an indispensable heart inducer. A...
Cardiac lineage specification in the mouse is controlled by TGFβ and WNT signaling. From fly to fish, BMP has been identified as an indispensable heart inducer. A detailed analysis of the role of Bmp4 and its effectors Smad1/5, however, was still missing. We show that Bmp4 induces cardiac mesoderm formation in murine embryonic stem cells in vitro. Bmp4 first activates Wnt3 and upregulates Nodal. pSmad1/5 and the WNT effector Tcf3 form a complex, and together with pSmad2/3 activate mesoderm enhancers and Eomes. They then cooperate with Eomes to consolidate the expression of many mesoderm factors, including T. Eomes and T form a positive- feedback loop and open additional enhancers regulating early mesoderm genes, including the transcription factor Mesp1, establishing the cardiac mesoderm lineage. In parallel, the neural fate is suppressed. Our data confirm the pivotal role of Bmp4 in cardiac mesoderm formation in the mouse. We describe in detail the consecutive and cooperative actions of three signaling pathways, BMP, WNT and Nodal, and their effector transcription factors, during cardiac mesoderm specification.
Topics: Mice; Animals; Cell Differentiation; Heart; Transcription Factors; Mesoderm; Transforming Growth Factor beta; Wnt Signaling Pathway; Bone Morphogenetic Protein 4
PubMed: 37082965
DOI: 10.1242/dev.201450 -
Seminars in Cell & Developmental Biology Sep 2023In development, tissue shape changes and gene expression patterns give rise to morphogenesis. Understanding tissue shape changes requires the analysis of mechanical... (Review)
Review
In development, tissue shape changes and gene expression patterns give rise to morphogenesis. Understanding tissue shape changes requires the analysis of mechanical properties of the tissue such as tissue rigidity, cell influx from neighboring tissues, cell shape changes and cell proliferation. Local and global gene expression patterns can be influenced by neighbor exchange and tissue shape changes. Here we review recent studies on the mechanisms for tissue elongation and its influences on dynamic gene expression patterns by focusing on vertebrate somitogenesis. We first introduce mechanical and biochemical properties of the segmenting tissue that drive tissue elongation. Then, we discuss patterning in the presence of cell mixing, scaling of signaling gradients, and dynamic phase waves of rhythmic gene expression under tissue shape changes. We also highlight the importance of theoretical approaches to address the relation between tissue shape changes and patterning.
Topics: Somites; Body Patterning; Morphogenesis; Embryonic Development; Gene Expression; Gene Expression Regulation, Developmental; Mesoderm
PubMed: 36631335
DOI: 10.1016/j.semcdb.2022.12.009 -
Seminars in Cell & Developmental Biology Jul 2022Human pluripotent stem cells can differentiate into any cell type given appropriate signals and hence have been used to research early human development of many tissues... (Review)
Review
Human pluripotent stem cells can differentiate into any cell type given appropriate signals and hence have been used to research early human development of many tissues and diseases. Here, we review the major biological factors that regulate cartilage and bone development through the three main routes of neural crest, lateral plate mesoderm and paraxial mesoderm. We examine how these routes have been used in differentiation protocols that replicate skeletal development using human pluripotent stem cells and how these methods have been refined and improved over time. Finally, we discuss how pluripotent stem cells can be employed to understand human skeletal genetic diseases with a developmental origin and phenotype, and how developmental protocols have been applied to gain a better understanding of these conditions.
Topics: Bone and Bones; Cartilage; Cell Differentiation; Humans; Mesoderm; Neural Crest; Pluripotent Stem Cells
PubMed: 34949507
DOI: 10.1016/j.semcdb.2021.11.024 -
Reproductive Toxicology (Elmsford, N.Y.) Jan 2022Embryonic stem cell differentiation models have increasingly been applied in non-animal test systems for developmental toxicity. After the initial focus on cardiac... (Review)
Review
Embryonic stem cell differentiation models have increasingly been applied in non-animal test systems for developmental toxicity. After the initial focus on cardiac differentiation, attention has also included an array of neuro-ectodermal differentiation routes. Alternative differentiation routes in the mesodermal and endodermal germ lines have received less attention. This review provides an inventory of achievements in the latter areas of embryonic stem cell differentiation, with a view to possibilities for their use in non-animal test systems in developmental toxicology. This includes murine and human stem cell differentiation models, and also gains information from the field of stem cell use in regenerative medicine. Endodermal stem cell derivatives produced in vitro include hepatocytes, pancreatic cells, lung epithelium, and intestinal epithelium, and mesodermal derivatives include cardiac muscle, osteogenic, vascular and hemopoietic cells. This inventory provides an overview of studies on the different cell types together with biomarkers and culture conditions that stimulate these differentiation routes from embryonic stem cells. These models may be used to expand the spectrum of embryonic stem cell based new approach methodologies in non-animal developmental toxicity testing.
Topics: Animals; Cell Differentiation; Embryonic Stem Cells; Endoderm; Humans; Mesoderm; Models, Biological; Toxicity Tests
PubMed: 34861400
DOI: 10.1016/j.reprotox.2021.11.009 -
The International Journal of... Aug 2020Chronic Obstructive Pulmonary disease (COPD) involves airway inflammation and remodeling leading to small airways disease and emphysema, which results in irreversible... (Review)
Review
Chronic Obstructive Pulmonary disease (COPD) involves airway inflammation and remodeling leading to small airways disease and emphysema, which results in irreversible airflow obstruction. During lung development, reciprocal interactions between the endoderm and mesoderm (epithelial-mesenchymal trophic unit (EMTU)) are essential for morphogenetic cues that direct cell proliferation, differentiation, and extracellular (ECM) production. In COPD, a significant number of the inflammation and remodeling mediators resemble those released during lung development, which has led to the hypothesis that aberrant activation of the EMTU may occur in the disease. Studies assessing lung epithelial and fibroblast function in COPD, have been primarily focused on monoculture studies. To capture the in vivo environment of the human lung and aid in the understanding of mechanisms and mediators involved in abnormal epithelial-fibroblast communication in COPD, complex co-culture models are required. In this review, we describe the studies that have used co-culture models to assess epithelial-fibroblast interactions and their role in the pathogenesis of COPD.
Topics: Cell Differentiation; Cell Proliferation; Coculture Techniques; Cytokines; Epithelial Cells; Fibroblasts; Humans; In Vitro Techniques; Inflammation; Lung; Mesoderm; Organoids; Pulmonary Disease, Chronic Obstructive
PubMed: 32473924
DOI: 10.1016/j.biocel.2020.105775