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Developmental Cell Jun 2023Mesenchymal-epithelial transition (MET) is a critical process in development, guiding tissue morphogenesis. In this issue of Developmental Cell, two studies, one by...
Mesenchymal-epithelial transition (MET) is a critical process in development, guiding tissue morphogenesis. In this issue of Developmental Cell, two studies, one by Gredler et al. and one by Abboud Asleh et al., reveal how multicellular rosettes critically contribute to MET in earliest notochord and lateral plate mesoderm formation, respectively.
Topics: Cell Differentiation; Mesoderm; Morphogenesis; Gastrula; Gastrulation
PubMed: 37279697
DOI: 10.1016/j.devcel.2023.04.018 -
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 -
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 -
Stem Cell Reports Jan 2024While studied extensively in model systems, human gastrulation remains obscure. The scarcity of fetal biological material as well as ethical considerations limit our...
While studied extensively in model systems, human gastrulation remains obscure. The scarcity of fetal biological material as well as ethical considerations limit our understanding of this process. In vitro attachment of natural blastocysts shed light on aspects of the second week of human development in the absence of the morphological manifestation of gastrulation. Stem cell-derived blastocyst models, blastoids, provide the opportunity to reconstitute pre- to post-implantation development in vitro. Here we show that upon in vitro attachment, human blastoids self-organize a BRA population and undergo gastrulation. Single-cell RNA sequencing of these models replicates the transcriptomic signature of the human gastrula. Analysis of developmental timing reveals that in both blastoid models and natural human embryos, the onset of gastrulation as defined by molecular markers, can be traced to timescales equivalent to 12 days post fertilization. In all, natural human embryos and blastoid models self-organize primitive streak and mesoderm derivatives upon in vitro attachment.
Topics: Humans; Gastrulation; Gastrula; Embryonic Development; Blastocyst; Mesoderm
PubMed: 38101401
DOI: 10.1016/j.stemcr.2023.11.005 -
Philosophical Transactions of the Royal... Dec 2022During the early development of Placentalia, a distinctive projection emerges at the posterior embryonic-extraembryonic interface of the conceptus; its fingerlike shape... (Review)
Review
During the early development of Placentalia, a distinctive projection emerges at the posterior embryonic-extraembryonic interface of the conceptus; its fingerlike shape presages maturation into the placental umbilical cord, whose major role is to shuttle fetal blood to and from the chorion for exchange with the mother during pregnancy. Until recently, the biology of the cord's vital vascular anlage, called the body stalk/allantois in humans and simply the allantois in rodents, has been largely unknown. Here, new insights into the development of the mouse allantois are featured, from its origin and mechanism of arterial patterning through its union with the chorion. Key to generating the allantois and its critical functions are the primitive streak and visceral endoderm, which together are sufficient to create the entire fetal-placental connection. Their newly discovered roles at the embryonic-extraembryonic interface challenge conventional wisdom, including the physical limits of the primitive streak, its function as sole purveyor of mesoderm in the mouse, potency of visceral endoderm, and the putative role of the allantois in the germ line. With this working model of allantois development, understanding a plethora of hitherto poorly understood orphan diseases in humans is now within reach. This article is part of the theme issue 'Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom'.
Topics: Allantois; Animals; Embryo, Mammalian; Female; Humans; Mesoderm; Mice; Placenta; Pregnancy; Primitive Streak
PubMed: 36252214
DOI: 10.1098/rstb.2021.0251 -
Nature Jan 2023Sequential segmentation creates modular body plans of diverse metazoan embryos. Somitogenesis establishes the segmental pattern of the vertebrate body axis. A molecular...
Sequential segmentation creates modular body plans of diverse metazoan embryos. Somitogenesis establishes the segmental pattern of the vertebrate body axis. A molecular segmentation clock in the presomitic mesoderm sets the pace of somite formation. However, how cells are primed to form a segment boundary at a specific location remains unclear. Here we developed precise reporters for the clock and double-phosphorylated Erk (ppErk) gradient in zebrafish. We show that the Her1-Her7 oscillator drives segmental commitment by periodically lowering ppErk, therefore projecting its oscillation onto the ppErk gradient. Pulsatile inhibition of the ppErk gradient can fully substitute for the role of the clock, and kinematic clock waves are dispensable for sequential segmentation. The clock functions upstream of ppErk, which in turn enables neighbouring cells to discretely establish somite boundaries in zebrafish. Molecularly divergent clocks and morphogen gradients were identified in sequentially segmenting species. Our findings imply that versatile clocks may establish sequential segmentation in diverse species provided that they inhibit gradients.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Body Patterning; Gene Expression Regulation, Developmental; Somites; Zebrafish; Zebrafish Proteins; Biological Clocks; Periodicity; Extracellular Signal-Regulated MAP Kinases
PubMed: 36517597
DOI: 10.1038/s41586-022-05527-x -
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 -
Molecular Medicine Reports Sep 2021Ghrelin, an orexigenic hormone, is a peptide that binds to the growth hormone secretagogue receptor; it is secreted mainly by enteroendocrine cells in the oxyntic glands... (Review)
Review
Ghrelin, an orexigenic hormone, is a peptide that binds to the growth hormone secretagogue receptor; it is secreted mainly by enteroendocrine cells in the oxyntic glands of the stomach. Ghrelin serves a role in both local and systemic physiological processes, and is implicated in various pathologies, including neoplasia, with tissue expression in several types of malignancies in both and studies. However, the precise implications of the ghrelin axis in metastasis, invasion and cancer progression regulation has yet to be established. In the case of gastrointestinal (GI) tract malignancies, ghrelin has shown potential to become a prognostic factor or even a therapeutic target, although data in the literature are inconsistent and unsystematic, with reports untailored to a specific histological subtype of cancer or a particular localization. The evaluation of immunohistochemical expression shows a limited outlook owing to the low number of cases analyzed, and analyses have conflicting data regarding differences in ghrelin serum levels in patients with cancer. The aim of this review was to examine the relationship between ghrelin and GI tract malignancies to demonstrate the inconsistencies in current results and to highlight its clinical significance in the outcome of these patients.
Topics: Animals; Gastrointestinal Neoplasms; Ghrelin; Humans; Mesoderm; Neuroendocrine Tumors; Receptors, Ghrelin; Signal Transduction
PubMed: 34296307
DOI: 10.3892/mmr.2021.12302 -
Nature Communications Aug 2020The periodic cartilage and smooth muscle structures in mammalian trachea are derived from tracheal mesoderm, and tracheal malformations result in serious respiratory...
The periodic cartilage and smooth muscle structures in mammalian trachea are derived from tracheal mesoderm, and tracheal malformations result in serious respiratory defects in neonates. Here we show that canonical Wnt signaling in mesoderm is critical to confer trachea mesenchymal identity in human and mouse. At the initiation of tracheal development, endoderm begins to express Nkx2.1, and then mesoderm expresses the Tbx4 gene. Loss of β-catenin in fetal mouse mesoderm causes loss of Tbx4 tracheal mesoderm and tracheal cartilage agenesis. The mesenchymal Tbx4 expression relies on endodermal Wnt activation and Wnt ligand secretion but is independent of known Nkx2.1-mediated respiratory development, suggesting that bidirectional Wnt signaling between endoderm and mesoderm promotes trachea development. Activating Wnt, Bmp signaling in mouse embryonic stem cell (ESC)-derived lateral plate mesoderm (LPM) generates tracheal mesoderm containing chondrocytes and smooth muscle cells. For human ESC-derived LPM, SHH activation is required along with WNT to generate proper tracheal mesoderm. Together, these findings may contribute to developing applications for human tracheal tissue repair.
Topics: Animals; Cell Differentiation; Cells, Cultured; Endoderm; Gene Expression Regulation, Developmental; Human Embryonic Stem Cells; Humans; Mesoderm; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Mouse Embryonic Stem Cells; T-Box Domain Proteins; Thyroid Nuclear Factor 1; Trachea; Wnt Signaling Pathway; beta Catenin
PubMed: 32855415
DOI: 10.1038/s41467-020-17969-w -
Journal of Anatomy Sep 2022In the thorax of higher vertebrates, ribs and intercostal muscles play a decisive role in stability and respiratory movements of the body wall. They are derivatives of...
In the thorax of higher vertebrates, ribs and intercostal muscles play a decisive role in stability and respiratory movements of the body wall. They are derivatives of the somites, the ribs originating in the sclerotome and the intercostal muscles originating in the myotome. During thorax development, ribs and intercostal muscles extend into the lateral plate mesoderm and eventually contact the sternum during ventral closure. Here, we give a detailed description of the morphogenesis of ribs and thoracic muscles in the chicken embryo (Gallus gallus). Using Alcian blue staining as well as Sox9 and Desmin whole-mount immunohistochemistry, we monitor synchronously the development of rib cartilage and intercostal muscle anlagen. We show that the muscle anlagen precede the rib anlagen during ventrolateral extension, which is in line with the inductive role of the myotome in rib differentiation. Our studies furthermore reveal the temporary formation of a previously unknown eighth rib in the chicken embryonic thorax.
Topics: Animals; Chick Embryo; Chickens; Intercostal Muscles; Muscle, Skeletal; Ribs; Somites
PubMed: 35751554
DOI: 10.1111/joa.13716