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Developmental Biology May 2022T is the founding member of the T-box family of transcription factors; family members are critical for cell fate decisions and tissue morphogenesis throughout the animal...
T is the founding member of the T-box family of transcription factors; family members are critical for cell fate decisions and tissue morphogenesis throughout the animal kingdom. T is expressed in the primitive streak and notochord with mouse mutant studies revealing its critical role in mesoderm formation in the primitive streak and notochord integrity. We previously demonstrated that misexpression of Tbx6 in the paraxial and lateral plate mesoderm results in embryos resembling Tbx15 and Tbx18 nulls. This, together with results from in vitro transcriptional assays, suggested that ectopically expressed Tbx6 can compete with endogenously expressed Tbx15 and Tbx18 at the binding sites of target genes. Since T-box proteins share a similar DNA binding domain, we hypothesized that misexpressing T in the paraxial and lateral plate mesoderm would also interfere with the endogenous Tbx15 and Tbx18, causing embryonic phenotypes resembling those seen upon Tbx6 expression in the somites and limbs. Interestingly, ectopic T expression led to distinct embryonic phenotypes, specifically, reduced-sized somites in embryos expressing the highest levels of T, which ultimately affects axis length and neural tube morphogenesis. We further demonstrate that ectopic T leads to ectopic expression of Tbx6 and Mesogenin 1, known targets of T. These results suggests that ectopic T expression contributes to the phenotype by activating its own targets rather than via a straight competition with endogenous T-box factors.
Topics: Animals; Ectopic Gene Expression; Embryonic Development; Gene Expression Regulation, Developmental; Mesoderm; Mice; Somites; T-Box Domain Proteins
PubMed: 35276131
DOI: 10.1016/j.ydbio.2022.02.010 -
Mechanisms of Development Apr 2017Adhesion differences are the main driver of cell sorting and related processes such as boundary formation or tissue positioning. In the early amphibian embryo, graded... (Review)
Review
Adhesion differences are the main driver of cell sorting and related processes such as boundary formation or tissue positioning. In the early amphibian embryo, graded variations in cadherin density and localized expression of adhesion-modulating factors are associated with regional differences in adhesive properties including overall adhesion strength. The role of these differences in embryonic boundary formation has not been studied extensively, but available evidence suggests that adhesion strength differentials are not essential. On the other hand, the inside-out positioning of the germ layers is correlated with adhesion strength, although the biological significance of this effect is unclear. By contrast, the positioning of dorsal mesoderm tissues along the anterior-posterior body axis is essential for axis elongation, but the underlying sorting mechanism is not correlated with adhesion strength, and may rely on specific cell adhesion. Formation of the ectoderm-mesoderm boundary is the best understood sorting related process in the frog embryo. It relies on contact-induced cell repulsion at the tissue interface, driven by Eph-ephrin signaling and paraxial protocadherin-dependent self/non-self recognition.
Topics: Animals; Cadherins; Cell Adhesion; Cell Communication; Cell Movement; Ectoderm; Embryo, Nonmammalian; Endoderm; Ephrins; Gene Expression Regulation, Developmental; Mesoderm; Receptors, Eph Family; Signal Transduction; Xenopus Proteins; Xenopus laevis
PubMed: 27697520
DOI: 10.1016/j.mod.2016.09.003 -
International Journal of Molecular... Jan 2021Skeletal disorders, such as osteoarthritis and bone fractures, are among the major conditions that can compromise the quality of daily life of elderly individuals. To... (Review)
Review
Skeletal disorders, such as osteoarthritis and bone fractures, are among the major conditions that can compromise the quality of daily life of elderly individuals. To treat them, regenerative therapies using skeletal cells have been an attractive choice for patients with unmet clinical needs. Currently, there are two major strategies to prepare the cell sources. The first is to use induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs), which can recapitulate the skeletal developmental process and differentiate into various skeletal cells. Skeletal tissues are derived from three distinct origins: the neural crest, paraxial mesoderm, and lateral plate mesoderm. Thus, various protocols have been proposed to recapitulate the sequential process of skeletal development. The second strategy is to extract stem cells from skeletal tissues. In addition to mesenchymal stem/stromal cells (MSCs), multiple cell types have been identified as alternative cell sources. These cells have distinct multipotent properties allowing them to differentiate into skeletal cells and various potential applications for skeletal regeneration. In this review, we summarize state-of-the-art research in stem cell differentiation based on the understanding of embryogenic skeletal development and stem cells existing in skeletal tissues. We then discuss the potential applications of these cell types for regenerative medicine.
Topics: Animals; Bone Development; Bone and Bones; Cell Differentiation; Disease Models, Animal; Embryo, Mammalian; Embryonic Development; Embryonic Stem Cells; Fractures, Bone; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cells; Mesoderm; Neural Crest; Osteoarthritis; Osteoblasts; Regenerative Medicine; Stem Cell Transplantation
PubMed: 33573345
DOI: 10.3390/ijms22031404 -
Cold Spring Harbor Protocols Nov 2022Marginal zone explants from embryos can be used to expose cell behaviors and tissue movements that normally operate in dorsal tissues. Dorsal explants comprise the...
Marginal zone explants from embryos can be used to expose cell behaviors and tissue movements that normally operate in dorsal tissues. Dorsal explants comprise the diverse set of progenitor cells found in dorsal tissues including mesendoderm, head mesoderm, prechordal mesoderm, endoderm with bottle cells, axial mesoderm of the prospective notochord, paraxial mesoderm of the somites, lateral plate mesoderm, neural ectoderm, and ectoderm. Unlike an organoid, the dorsal marginal zone (DMZ) explant is "organotypic" in that microsurgery does not disrupt native tissue organization beyond manipulations needed to dissect the tissue from the embryo. An organotypic early gastrula DMZ explant preserves boundaries and close tissue associations in the native marginal zone. Depending on the stage, patterning and cell identities can be maintained in explants and tissue isolates. Local cell movements and behaviors may also be preserved; however, the large-scale biomechanical impact of their collective movements may be altered from those in the native marginal zone. For instance, involution is typically inhibited in the DMZ explant, precluding the two-layer association of mesoderm and prospective neural ectoderm normally achieved during gastrulation. DMZ explants may be mounted and imaged in a variety of ways, exposing interesting cell behaviors or collective movements such as mediolateral cell intercalation in the axial and paraxial mesoderm, apical constriction of bottle cells, and directional migration of mesendoderm. The flattened DMZ explant can also be used to study emergence of new tissue-defining boundaries such as the notochord-somite boundary, the ectoderm-mesoderm boundary, and the mesendoderm-mesoderm boundary.
Topics: Animals; Gastrula; Prospective Studies; Mesoderm; Xenopus laevis; Ectoderm
PubMed: 35577522
DOI: 10.1101/pdb.prot097360 -
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 -
Nature Jun 2023The development of paired appendages was a key innovation during evolution and facilitated the aquatic to terrestrial transition of vertebrates. Largely derived from the...
The development of paired appendages was a key innovation during evolution and facilitated the aquatic to terrestrial transition of vertebrates. Largely derived from the lateral plate mesoderm (LPM), one hypothesis for the evolution of paired fins invokes derivation from unpaired median fins via a pair of lateral fin folds located between pectoral and pelvic fin territories. Whilst unpaired and paired fins exhibit similar structural and molecular characteristics, no definitive evidence exists for paired lateral fin folds in larvae or adults of any extant or extinct species. As unpaired fin core components are regarded as exclusively derived from paraxial mesoderm, any transition presumes both co-option of a fin developmental programme to the LPM and bilateral duplication. Here, we identify that the larval zebrafish unpaired pre-anal fin fold (PAFF) is derived from the LPM and thus may represent a developmental intermediate between median and paired fins. We trace the contribution of LPM to the PAFF in both cyclostomes and gnathostomes, supporting the notion that this is an ancient trait of vertebrates. Finally, we observe that the PAFF can be bifurcated by increasing bone morphogenetic protein signalling, generating LPM-derived paired fin folds. Our work provides evidence that lateral fin folds may have existed as embryonic anlage for elaboration to paired fins.
Topics: Animals; Animal Fins; Biological Evolution; Larva; Mesoderm; Zebrafish; Bone Morphogenetic Proteins
PubMed: 37225983
DOI: 10.1038/s41586-023-06100-w -
Nature Communications Feb 2021Somites arising from paraxial mesoderm are a hallmark of the segmented vertebrate body plan. They form sequentially during axis extension and generate musculoskeletal...
Somites arising from paraxial mesoderm are a hallmark of the segmented vertebrate body plan. They form sequentially during axis extension and generate musculoskeletal cell lineages. How paraxial mesoderm becomes regionalised along the axis and how this correlates with dynamic changes of chromatin accessibility and the transcriptome remains unknown. Here, we report a spatiotemporal series of ATAC-seq and RNA-seq along the chick embryonic axis. Footprint analysis shows differential coverage of binding sites for several key transcription factors, including CDX2, LEF1 and members of HOX clusters. Associating accessible chromatin with nearby expressed genes identifies cis-regulatory elements (CRE) for TCF15 and MEOX1. We determine their spatiotemporal activity and evolutionary conservation in Xenopus and human. Epigenome silencing of endogenous CREs disrupts TCF15 and MEOX1 gene expression and recapitulates phenotypic abnormalities of anterior-posterior axis extension. Our integrated approach allows dissection of paraxial mesoderm regulatory circuits in vivo and has implications for investigating gene regulatory networks.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; CDX2 Transcription Factor; Cell Lineage; Chick Embryo; Chromatin; Female; Gastrulation; Gene Expression Regulation, Developmental; Homeodomain Proteins; Lymphoid Enhancer-Binding Factor 1; Mesoderm; Regulatory Sequences, Nucleic Acid; Somites; Transcription Factors; Transcriptome; Xenopus laevis
PubMed: 33608545
DOI: 10.1038/s41467-021-21426-7 -
Science Advances Jan 2024Spatiotemporal patterns widely occur in biological, chemical, and physical systems. Particularly, embryonic development displays a diverse gamut of repetitive patterns... (Review)
Review
Spatiotemporal patterns widely occur in biological, chemical, and physical systems. Particularly, embryonic development displays a diverse gamut of repetitive patterns established in many tissues and organs. Branching treelike structures in lungs, kidneys, livers, pancreases, and mammary glands as well as digits and bones in appendages, teeth, and palates are just a few examples. A fascinating instance of repetitive patterning is the sequential segmentation of the primary body axis, which is conserved in all vertebrates and many arthropods and annelids. In these species, the body axis elongates at the posterior end of the embryo containing an unsegmented tissue. Meanwhile, segments sequentially bud off from the anterior end of the unsegmented tissue, laying down an exquisite repetitive pattern and creating a segmented body plan. In vertebrates, the paraxial mesoderm is sequentially divided into somites. In this review, we will discuss the most prominent models, the most puzzling experimental data, and outstanding questions in vertebrate somite segmentation.
Topics: Animals; Body Patterning; Somites; Mesoderm; Vertebrates; Embryonic Development; Gene Expression Regulation, Developmental
PubMed: 38277458
DOI: 10.1126/sciadv.adk8937 -
Developmental Biology Sep 2017The physical basis of morphogenesis is a fascinating concern that has been a longstanding interest of developmental biologists. In this review, I attempt to incorporate... (Review)
Review
The physical basis of morphogenesis is a fascinating concern that has been a longstanding interest of developmental biologists. In this review, I attempt to incorporate earlier and recent biophysical concepts and data to explain basic features of early limb bud morphogenesis. In particular, I discuss the influence of mesenchymal cohesion and physical properties that might contribute to phase separation of the bud from the lateral plate, the possibility that the early dorsoventral limb bud axis is moulded by the surface ectoderm, and endogenous electric fields that might contribute to oriented cell movements which generate the early limb bud. A combination of quantitative biophysical experimentation and modelling will likely advance this field.
Topics: Animals; Biophysical Phenomena; Cell Movement; Cell Polarity; Electricity; Limb Buds; Mesoderm; Morphogenesis
PubMed: 28669818
DOI: 10.1016/j.ydbio.2017.06.034 -
Developmental Cell Jul 2019Endothelial cells (ECs), which line blood and lymphatic vessels, are generally described to come from the lateral plate mesoderm despite experimental evidence for a...
Endothelial cells (ECs), which line blood and lymphatic vessels, are generally described to come from the lateral plate mesoderm despite experimental evidence for a broader source of origin, including the paraxial mesoderm (PXM). Current dogma suggests that following specification from mesoderm, local environmental cues establish the distinct molecular and functional characteristics of ECs in different vascular beds. Here we present evidence to challenge this view, showing that lymphatic EC fate is imprinted during transition through the PXM lineage. We show that PXM-derived cells form the lymphatic endothelium of multiple organs and tissues, with a more restricted contribution to blood vessel endothelium. By deleting Prox1 specifically in PXM-derived cells, we show that this lineage is indispensable for lymphatic vessel development. Collectively, our data establish lineage history as a critical determinant of EC specialization, a finding with broad implications for our understanding of vascular development and heterogeneity.
Topics: Animals; Cell Differentiation; Cell Lineage; Endothelium, Lymphatic; Lymphangiogenesis; Lymphatic Vessels; Mesoderm; Mice; Phenotype; Transcription Factors
PubMed: 31130354
DOI: 10.1016/j.devcel.2019.04.034