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Developmental Cell Jun 2023Mesenchymal-epithelial transitions are fundamental drivers of development and disease, but how these behaviors generate epithelial structure is not well understood....
Mesenchymal-epithelial transitions are fundamental drivers of development and disease, but how these behaviors generate epithelial structure is not well understood. Here, we show that mesenchymal-epithelial transitions promote epithelial organization in the mouse node and notochordal plate through the assembly and radial intercalation of three-dimensional rosettes. Axial mesoderm rosettes acquire junctional and apical polarity, develop a central lumen, and dynamically expand, coalesce, and radially intercalate into the surface epithelium, converting mesenchymal-epithelial transitions into higher-order tissue structure. In mouse Par3 mutants, axial mesoderm rosettes establish central tight junction polarity but fail to form an expanded apical domain and lumen. These defects are associated with altered rosette dynamics, delayed radial intercalation, and formation of a small, fragmented surface epithelial structure. These results demonstrate that three-dimensional rosette behaviors translate mesenchymal-epithelial transitions into collective radial intercalation and epithelial formation, providing a strategy for building epithelial sheets from individual self-organizing units in the mammalian embryo.
Topics: Animals; Mice; Mesoderm; Epithelium; Cell Differentiation; Embryo, Mammalian; Morphogenesis; Mammals
PubMed: 37080203
DOI: 10.1016/j.devcel.2023.03.018 -
Hepatology Communications Mar 2021The hepatic mesenchyme has been studied extensively in the context of liver fibrosis; however, much less is known regarding the role of mesenchymal cells during liver... (Review)
Review
The hepatic mesenchyme has been studied extensively in the context of liver fibrosis; however, much less is known regarding the role of mesenchymal cells during liver regeneration. As our knowledge of the cellular and molecular mechanisms driving hepatic regeneration deepens, the key role of the mesenchymal compartment during the regenerative response has been increasingly appreciated. Single-cell genomics approaches have recently uncovered both spatial and functional zonation of the hepatic mesenchyme in homeostasis and following liver injury. Here we discuss how the use of preclinical models, from in vivo mouse models to organoid-based systems, are helping to shape our understanding of the role of the mesenchyme during liver regeneration, and how these approaches should facilitate the precise identification of highly targeted, pro-regenerative therapies for patients with liver disease.
Topics: Animals; Cells, Cultured; Hepatic Stellate Cells; Humans; Liver; Liver Diseases; Liver Regeneration; Mesoderm; Mice
PubMed: 33681672
DOI: 10.1002/hep4.1628 -
EMBO Reports Aug 2022Immigration of mesenchymal cells into the growing fin and limb buds drives distal outgrowth, with subsequent tensile forces between these cells essential for fin and...
Immigration of mesenchymal cells into the growing fin and limb buds drives distal outgrowth, with subsequent tensile forces between these cells essential for fin and limb morphogenesis. Morphogens derived from the apical domain of the fin, orientate limb mesenchyme cell polarity, migration, division and adhesion. The zebrafish mutant stomp displays defects in fin morphogenesis including blister formation and associated loss of orientation and adhesion of immigrating fin mesenchyme cells. Positional cloning of stomp identifies a mutation in the gene encoding the axon guidance ligand, Slit3. We provide evidence that Slit ligands derived from immigrating mesenchyme act via Robo receptors at the apical ectodermal ridge (AER) to promote release of sphingosine-1-phosphate (S1P). S1P subsequently diffuses back to the mesenchyme to promote their polarisation, orientation, positioning and adhesion to the interstitial matrix of the fin fold. We thus demonstrate the coordination of the Slit-Robo and S1P signalling pathways in fin fold morphogenesis. Our work introduces a mechanism regulating the orientation, positioning and adhesion of its constituent cells.
Topics: Animals; Gene Expression Regulation, Developmental; Intracellular Signaling Peptides and Proteins; Lysophospholipids; Mesoderm; Sphingosine; Zebrafish; Zebrafish Proteins
PubMed: 35679135
DOI: 10.15252/embr.202154464 -
Seminars in Cell & Developmental Biology Jul 2022The discovery of mesoderm inducing signals helped usher in the era of molecular developmental biology, and today the mechanisms of mesoderm induction and patterning are... (Review)
Review
The discovery of mesoderm inducing signals helped usher in the era of molecular developmental biology, and today the mechanisms of mesoderm induction and patterning are still intensely studied. Mesoderm induction begins during gastrulation, but recent evidence in vertebrates shows that this process continues after gastrulation in a group of posteriorly localized cells called neuromesodermal progenitors (NMPs). NMPs reside within the post-gastrulation embryonic structure called the tailbud, where they make a lineage decision between ectoderm (spinal cord) and mesoderm. The majority of NMP-derived mesoderm generates somites, but also contributes to lateral mesoderm fates such as endothelium. The discovery of NMPs provides a new paradigm in which to study vertebrate mesoderm induction. This review will discuss mechanisms of mesoderm induction within NMPs, and how they have informed our understanding of mesoderm induction more broadly within vertebrates as well as animal species outside of the vertebrate lineage. Special focus will be given to the signaling networks underlying NMP-derived mesoderm induction and patterning, as well as emerging work on the significance of partial epithelial-mesenchymal states in coordinating cell fate and morphogenesis.
Topics: Animals; Body Patterning; Cell Differentiation; Gastrulation; Gene Expression Regulation, Developmental; Mesoderm; Somites
PubMed: 34840081
DOI: 10.1016/j.semcdb.2021.11.010 -
FEBS Letters Dec 2019The haematopoietic system is established during embryonic life through a series of developmental steps that culminates with the generation of haematopoietic stem cells.... (Review)
Review
The haematopoietic system is established during embryonic life through a series of developmental steps that culminates with the generation of haematopoietic stem cells. Characterisation of the transcriptional network that regulates blood cell emergence has led to the identification of transcription factors essential for this process. Among the many factors wired within this complex regulatory network, ETV2, SCL and RUNX1 are the central components. All three factors are absolutely required for blood cell generation, each one controlling a precise step of specification from the mesoderm germ layer to fully functional blood progenitors. Insight into the transcriptional control of blood cell emergence has been used for devising protocols to generate blood cells de novo, either through reprogramming of somatic cells or through forward programming of pluripotent stem cells. Interestingly, the physiological process of blood cell generation and its laboratory-engineered counterpart have very little in common.
Topics: Blood Cells; Cell Differentiation; Cellular Reprogramming; Core Binding Factor Alpha 2 Subunit; Hematopoietic Stem Cells; Humans; Mesoderm; Pluripotent Stem Cells; T-Cell Acute Lymphocytic Leukemia Protein 1; Transcription Factors; Transcriptional Activation
PubMed: 31432499
DOI: 10.1002/1873-3468.13585 -
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 -
Progress in Biophysics and Molecular... Dec 2021If you cut a mobius strip in half, the edges form a Trefoil Knot, which can be untied to form a circle, proving it's a true mathematical knot. The cell is a homologue of... (Review)
Review
If you cut a mobius strip in half, the edges form a Trefoil Knot, which can be untied to form a circle, proving it's a true mathematical knot. The cell is a homologue of the mathematical knot since it, too, must be able to unknot itself to form the egg and sperm meiotically in order to reproduce. The homology between a knot and a cell is thought-provoking biologically because the Trefoil Knot is a metaphor for the endoderm, ectoderm and mesoderm, the three germ layers of the gastrula that ultimately produce the embryo, beginning with the zygote. Upon further consideration, the cell membrane is like a mobius strip, forming one continuous surface between the inner environment of the cell and the outer environment. However, it is not formed by taking a circular surface, cutting it, twisting it and attaching the two ends as you would conventionally to form a mobius strip. Conversely, David Bohm's Explicate Order forms a boundary with the Implicate Order. That lipid boundary is the prima facie mobius strip that divides the infinite surface of the Implicate Order into inside and outside by 'recalling' its pre-adapted state as lipid molecules before there was an inside or outside.
Topics: Ectoderm; Endoderm; Gastrula; Mesoderm
PubMed: 34364909
DOI: 10.1016/j.pbiomolbio.2021.08.001 -
Developmental Dynamics : An Official... Nov 2021Nephron progenitor cells (NPCs) undergo a stepwise process to generate all mature nephron structures. Mesenchymal to epithelial transition (MET) is considered a...
BACKGROUND
Nephron progenitor cells (NPCs) undergo a stepwise process to generate all mature nephron structures. Mesenchymal to epithelial transition (MET) is considered a multistep process of NPC differentiation to ensure progressive establishment of new nephrons. However, despite this important role, to date, no marker for NPCs undergoing MET in the nephron exists.
RESULTS
Here, we identify LGR6 as a NPC marker, expressed in very early cap mesenchyme, pre-tubular aggregates, renal vesicles, and in segments of S-shaped bodies, following the trajectory of MET. By using a lineage tracing approach in embryonic explants in combination with confocal imaging and single-cell RNA sequencing, we provide evidence for the multiple fates of LGR6+ cells during embryonic nephrogenesis. Moreover, by using long-term in vivo lineage tracing, we show that postnatal LGR6+ cells are capable of generating the multiple lineages of the nephrons.
CONCLUSIONS
Given the profound early mesenchymal expression and MET signature of LGR6 cells, together with the lineage tracing of mesenchymal LGR6 cells, we conclude that LGR6+ cells contribute to all nephrogenic segments by undergoing MET. LGR6+ cells can therefore be considered an early committed NPC population during embryonic and postnatal nephrogenesis with potential regenerative capability.
Topics: Cell Differentiation; Mesoderm; Nephrons; Organogenesis; Stem Cells
PubMed: 33848015
DOI: 10.1002/dvdy.346 -
Doklady Biological Sciences :... Dec 2023In Bilateria, the formation of the coelomic mesoderm occurs in various ways and is of great significance for comparative embryology and phylogeny. Several early...
In Bilateria, the formation of the coelomic mesoderm occurs in various ways and is of great significance for comparative embryology and phylogeny. Several early ontogenetic stages were studied in the brachiopod Coptothyris grayi by scanning electron microscopy and cytochemistry combined with confocal laser microscopy. Two sources of the mesoderm were observed to form simultaneously from the anterior and posterior walls of the archenteron at the gastrula stage. Both anterior and posterior rudiments form enterocoely as unpaired protrusions of the wall of the archenteron and are subsequently separated from it. The findings confirmed the previous data on enterocoely in brachiopods. Moreover, a dual origin of the coelomic mesoderm from an anterior and a posterior precursor was for the first time demonstrated for all brachiopods. Analysis of the literature showed that two sources of the coelomic mesoderm in ontogeny are characteristic of representatives of various groups of protostomes and deuterostomes. This fact may provide evidence for the earlier hypothesis of plesiomorphy of two sources of the mesoderm in Bilateria.
Topics: Animals; Invertebrates; Phylogeny; Mesoderm
PubMed: 38190043
DOI: 10.1134/S0012496623700837 -
Developmental Cell Feb 2023Organogenesis requires the orchestrated development of multiple cell lineages that converge, interact, and specialize to generate coherent functional structures,... (Review)
Review
Organogenesis requires the orchestrated development of multiple cell lineages that converge, interact, and specialize to generate coherent functional structures, exemplified by transformation of the cardiac crescent into a four-chambered heart. Cardiomyocytes originate from the first and second heart fields, which make different regional contributions to the definitive heart. In this review, a series of recent single-cell transcriptomic analyses, together with genetic tracing experiments, are discussed, providing a detailed panorama of the cardiac progenitor cell landscape. These studies reveal that first heart field cells originate in a juxtacardiac field adjacent to extraembryonic mesoderm and contribute to the ventrolateral side of the cardiac primordium. In contrast, second heart field cells are deployed dorsomedially from a multilineage-primed progenitor population via arterial and venous pole pathways. Refining our knowledge of the origin and developmental trajectories of cells that build the heart is essential to address outstanding challenges in cardiac biology and disease.
Topics: Heart; Myocytes, Cardiac; Cell Lineage; Mesoderm; Cell Differentiation
PubMed: 36809764
DOI: 10.1016/j.devcel.2023.01.010