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Cite this page: Hill, M.A. (2020, July 14) Embryology Mesoderm. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Mesoderm
10 Most Recent Papers
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<pubmed limit=5>Mesoderm Development</pubmed>
Analysis of extraembryonic mesodermal structure formation in the absence of morphological primitive streak
Dev Growth Differ. 2016 Aug;58(6):522-9. doi: 10.1111/dgd.12294. Epub 2016 Jun 8.
Jin JZ1, Zhu Y1, Warner D1, Ding J1.
During mouse gastrulation, the primitive streak is formed on the posterior side of the embryo. Cells migrate out of the primitive streak to form the future mesoderm and endoderm. Fate mapping studies revealed a group of cell migrate through the proximal end of the primitive streak and give rise to the extraembryonic mesoderm tissues such as the yolk sac blood islands and allantois. However, it is not clear whether the formation of a morphological primitive streak is required for the development of these extraembryonic mesodermal tissues. Loss of the Cripto gene in mice dramatically reduces, but does not completely abolish, Nodal activity leading to the absence of a morphological primitive streak. However, embryonic erythrocytes are still formed and assembled into the blood islands. In addition, Cripto mutant embryos form allantoic buds. However, Drap1 mutant embryos have excessive Nodal activity in the epiblast cells before gastrulation and form an expanded primitive streak, but no yolk sac blood islands or allantoic bud formation. Lefty2 embryos also have elevated levels of Nodal activity in the primitive streak during gastrulation, and undergo normal blood island and allantois formation. We therefore speculate that low level of Nodal activity disrupts the formation of morphological primitive streak on the posterior side, but still allows the formation of primitive streak cells on the proximal side, which give rise to the extraembryonic mesodermal tissues formation. Excessive Nodal activity in the epiblast at pre-gastrulation stage, but not in the primitive streak cells during gastrulation, disrupts extraembryonic mesoderm development. KEYWORDS: Cripto; Drap1; Lefty2; allantois; blood island; primitive streak PMID: 27273137 DOI: 10.1111/dgd.12294
BRACHYURY directs histone acetylation to target loci during mesoderm development
EMBO Rep. 2018 Jan;19(1):118-134. doi: 10.15252/embr.201744201. Epub 2017 Nov 15.
Beisaw A1,2,3, Tsaytler P1, Koch F1, Schmitz SU1, Melissari MT1, Senft AD1, Wittler L1, Pennimpede T1, Macura K1, Herrmann BG1,4, Grote P5,6.
T-box transcription factors play essential roles in multiple aspects of vertebrate development. Here, we show that cooperative function of BRACHYURY (T) with histone-modifying enzymes is essential for mouse embryogenesis. A single point mutation (TY88A) results in decreased histone 3 lysine 27 acetylation (H3K27ac) at T target sites, including the T locus, suggesting that T autoregulates the maintenance of its expression and functions by recruiting permissive chromatin modifications to putative enhancers during mesoderm specification. Our data indicate that T mediates H3K27ac recruitment through a physical interaction with p300. In addition, we determine that T plays a prominent role in the specification of hematopoietic and endothelial cell types. Hematopoietic and endothelial gene expression programs are disrupted in TY88A mutant embryos, leading to a defect in the differentiation of hematopoietic progenitors. We show that this role of T is mediated, at least in part, through activation of a distal Lmo2 enhancer. KEYWORDS: Brachyury ; Lmo2 ; H3K27 acetylation; T‐box factors; autoregulation PMID: 29141987 PMCID: PMC5757217 [Available on 2019-01-01] DOI: 10.15252/embr.201744201
STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm migration in the mouse embryo
Proc Natl Acad Sci U S A. 2017 Dec 19;114(51):E10928-E10936. doi: 10.1073/pnas.1713535114. Epub 2017 Dec 4.
Bazzi H1,2,3, Soroka E2,3, Alcorn HL4, Anderson KV1.
Regulated mesoderm migration is necessary for the proper morphogenesis and organ formation during embryonic development. Cell migration and its dependence on the cytoskeleton and signaling machines have been studied extensively in cultured cells; in contrast, remarkably little is known about the mechanisms that regulate mesoderm cell migration in vivo. Here, we report the identification and characterization of a mouse mutation in striatin-interacting protein 1 (Strip1) that disrupts migration of the mesoderm after the gastrulation epithelial-to-mesenchymal transition (EMT). STRIP1 is a core component of the biochemically defined mammalian striatin-interacting phosphatases and kinase (STRIPAK) complexes that appear to act through regulation of protein phosphatase 2A (PP2A), but their functions in mammals in vivo have not been examined. Strip1-null mutants arrest development at midgestation with profound disruptions in the organization of the mesoderm and its derivatives, including a complete failure of the anterior extension of axial mesoderm. Analysis of cultured mesoderm explants and mouse embryonic fibroblasts from null mutants shows that the mesoderm migration defect is correlated with decreased cell spreading, abnormal focal adhesions, changes in the organization of the actin cytoskeleton, and decreased velocity of cell migration. The results show that STRIPAK complexes are essential for cell migration and tissue morphogenesis in vivo. KEYWORDS: PP2A; STRIP1; STRIPAK; cell migration; mouse embryo PMID: 29203676 PMCID: PMC5754794 DOI: 10.1073/pnas.1713535114
A data analysis framework for biomedical big data: Application on mesoderm differentiation of human pluripotent stem cells
PLoS One. 2017 Jun 27;12(6):e0179613. doi: 10.1371/journal.pone.0179613. eCollection 2017.
Ulfenborg B1, Karlsson A2, Riveiro M2, Améen C3, Åkesson K3, Andersson CX3, Sartipy P1,4, Synnergren J1.
The development of high-throughput biomolecular technologies has resulted in generation of vast omics data at an unprecedented rate. This is transforming biomedical research into a big data discipline, where the main challenges relate to the analysis and interpretation of data into new biological knowledge. The aim of this study was to develop a framework for biomedical big data analytics, and apply it for analyzing transcriptomics time series data from early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. To this end, transcriptome profiling by microarray was performed on differentiating human pluripotent stem cells sampled at eleven consecutive days. The gene expression data was analyzed using the five-stage analysis framework proposed in this study, including data preparation, exploratory data analysis, confirmatory analysis, biological knowledge discovery, and visualization of the results. Clustering analysis revealed several distinct expression profiles during differentiation. Genes with an early transient response were strongly related to embryonic- and mesendoderm development, for example CER1 and NODAL. Pluripotency genes, such as NANOG and SOX2, exhibited substantial downregulation shortly after onset of differentiation. Rapid induction of genes related to metal ion response, cardiac tissue development, and muscle contraction were observed around day five and six. Several transcription factors were identified as potential regulators of these processes, e.g. POU1F1, TCF4 and TBP for muscle contraction genes. Pathway analysis revealed temporal activity of several signaling pathways, for example the inhibition of WNT signaling on day 2 and its reactivation on day 4. This study provides a comprehensive characterization of biological events and key regulators of the early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. The proposed analysis framework can be used to structure data analysis in future research, both in stem cell differentiation, and more generally, in biomedical big data analytics.
PMID: 28654683 PMCID: PMC5487013 DOI: 10.1371/journal.pone.0179613
An atlas of transcriptional, chromatin accessibility, and surface marker changes in human mesoderm development
Sci Data. 2016 Dec 20;3:160109. doi: 10.1038/sdata.2016.109.
Koh PW1, Sinha R2, Barkal AA2, Morganti RM2, Chen A2, Weissman IL2, Ang LT3, Kundaje A1, Loh KM2.
Mesoderm is the developmental precursor to myriad human tissues including bone, heart, and skeletal muscle. Unravelling the molecular events through which these lineages become diversified from one another is integral to developmental biology and understanding changes in cellular fate. To this end, we developed an in vitro system to differentiate human pluripotent stem cells through primitive streak intermediates into paraxial mesoderm and its derivatives (somites, sclerotome, dermomyotome) and separately, into lateral mesoderm and its derivatives (cardiac mesoderm). Whole-population and single-cell analyses of these purified populations of human mesoderm lineages through RNA-seq, ATAC-seq, and high-throughput surface marker screens illustrated how transcriptional changes co-occur with changes in open chromatin and surface marker landscapes throughout human mesoderm development. This molecular atlas will facilitate study of human mesoderm development (which cannot be interrogated in vivo due to restrictions on human embryo studies) and provides a broad resource for the study of gene regulation in development at the single-cell level, knowledge that might one day be exploited for regenerative medicine. PMID: 27996962 PMCID: PMC5170597 DOI: 10.1038/sdata.2016.109
Genesis. 2014 Jun;52(6):503-14. doi: 10.1002/dvg.22783. Epub 2014 May 5.
Follow your gut: relaying information from the site of left-right symmetry breaking in the mouse
Saijoh Y1, Viotti M, Hadjantonakis AK.
A central unresolved question in the molecular cascade that drives establishment of left-right (LR) asymmetry in vertebrates are the mechanisms deployed to relay information between the midline site of symmetry-breaking and the tissues which will execute a program of asymmetric morphogenesis. The cells located between these two distant locations must provide the medium for signal relay. Of these, the gut endoderm is an attractive candidate tissue for signal transmission since it comprises the epithelium that lies between the node, where asymmetry originates, and the lateral plate, where asymmetry can first be detected. Here, focusing on the mouse as a model, we review our current understanding and entertain open questions concerning the relay of LR information from its origin. © 2014 Wiley Periodicals, Inc. KEYWORDS: Connexin; LR asymmetry; Nodal, Sox17; extracellular matrix; gap junction intercellular communication; gastrulation; gut endoderm; lateral plate mesoderm; midline; mouse embryo; node
Salient features of the ciliated organ of asymmetry
Bioarchitecture. 2014 Jan-Feb;4(1):6-15. doi: 10.4161/bioa.28014. Epub 2014 Jan 31.
Many internal organs develop distinct left and right sides that are essential for their functions. In several vertebrate embryos, motile cilia generate an asymmetric fluid flow that plays an important role in establishing left-right (LR) signaling cascades. These 'LR cilia' are found in the ventral node and posterior notochordal plate in mammals, the gastrocoel roof plate in amphibians and Kupffer's vesicle in teleost fish. I consider these transient ciliated structures as the 'organ of asymmetry' that directs LR patterning of the developing embryo. Variations in size and morphology of the organ of asymmetry in different vertebrate species have raised questions regarding the fundamental features that are required for LR determination. Here, I review current models for how LR asymmetry is established in vertebrates, discuss the cellular architecture of the ciliated organ of asymmetry and then propose key features of this organ that are critical for orienting the LR body axis. KEYWORDS: Kupffer’s vesicle; Left-right asymmetry; calcium ion flux; cilia; congenital heart defects; gastrocoel roof plate; posterior notochordal plate
Mechanisms of left-right asymmetry and patterning: driver, mediator and responder
F1000Prime Rep. 2014 Dec 1;6:110. doi: 10.12703/P6-110. eCollection 2014.
Hamada H1, Tam PP2.
The establishment of a left-right (LR) organizer in the form of the ventral node is an absolute prerequisite for patterning the tissues on contralateral sides of the body of the mouse embryo. The experimental findings to date are consistent with a mechanistic paradigm that the laterality information, which is generated in the ventral node, elicits asymmetric molecular activity and cellular behaviour in the perinodal tissues. This information is then relayed to the cells in the lateral plate mesoderm (LPM) when the left-specific signal is processed and translated into LR body asymmetry. Here, we reflect on our current knowledge and speculate on the following: (a) what are the requisite anatomical and functional attributes of an LR organizer, (b) what asymmetric information is emanated from this organizer, and (c) how this information is transferred across the paraxial tissue compartment and elicits a molecular response specifically in the LPM.
PMID 25580264 [PubMed] PMCID: PMC4275019
Specialized filopodia direct long-range transport of SHH during vertebrate tissue patterning
A role for Vg1/Nodal signaling in specification of the intermediate mesoderm
Development. 2013 Apr;140(8):1819-29. doi: 10.1242/dev.093740.
Fleming BM, Yelin R, James RG, Schultheiss TM. Source Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
The intermediate mesoderm (IM) is the embryonic source of all kidney tissue in vertebrates. The factors that regulate the formation of the IM are not yet well understood. Through investigations in the chick embryo, the current study identifies and characterizes Vg1/Nodal signaling (henceforth referred to as 'Nodal-like signaling') as a novel regulator of IM formation. Excess Nodal-like signaling at gastrulation stages resulted in expansion of the IM at the expense of the adjacent paraxial mesoderm, whereas inhibition of Nodal-like signaling caused repression of IM gene expression. IM formation was sensitive to levels of the Nodal-like pathway co-receptor Cripto and was inhibited by a truncated form of the secreted molecule cerberus, which specifically blocks Nodal, indicating that the observed effects are specific to the Nodal-like branch of the TGFβ signaling pathway. The IM-promoting effects of Nodal-like signaling were distinct from the known effects of this pathway on mesoderm formation and left-right patterning, a finding that can be attributed to specific time windows for the activities of these Nodal-like functions. Finally, a link was observed between Nodal-like and BMP signaling in the induction of IM. Activation of IM genes by Nodal-like signaling required an active BMP signaling pathway, and Nodal-like signals induced phosphorylation of Smad1/5/8, which is normally associated with activation of BMP signaling pathways. We postulate that Nodal-like signaling regulates IM formation by modulating the IM-inducing effects of BMP signaling.
EphrinB/EphB signaling controls embryonic germ layer separation by contact-induced cell detachment
PLoS Biol. 2011 Mar;9(3):e1000597. Epub 2011 Mar 1.
Rohani N, Canty L, Luu O, Fagotto F, Winklbauer R. Source Department of Biology, McGill University, Montreal, Quebec, Canada.
Abstract BACKGROUND: The primordial organization of the metazoan body is achieved during gastrulation by the establishment of the germ layers. Adhesion differences between ectoderm, mesoderm, and endoderm cells could in principle be sufficient to maintain germ layer integrity and prevent intermixing. However, in organisms as diverse as fly, fish, or amphibian, the ectoderm-mesoderm boundary not only keeps these germ layers separated, but the ectoderm also serves as substratum for mesoderm migration, and the boundary must be compatible with repeated cell attachment and detachment.
PRINCIPAL FINDINGS: We show that localized detachment resulting from contact-induced signals at the boundary is at the core of ectoderm-mesoderm segregation. Cells alternate between adhesion and detachment, and detachment requires ephrinB/EphB signaling. Multiple ephrinB ligands and EphB receptors are expressed on each side of the boundary, and tissue separation depends on forward signaling across the boundary in both directions, involving partially redundant ligands and receptors and activation of Rac and RhoA.
CONCLUSION: This mechanism differs from a simple differential adhesion process of germ layer formation. Instead, it involves localized responses to signals exchanged at the tissue boundary and an attachment/detachment cycle which allows for cell migration across a cellular substratum.
PMID 21390298 [PubMed - in process] PMCID: PMC3046958
Brachyury establishes the embryonic mesodermal progenitor niche
Genes Dev. 2010 Dec 15;24(24):2778-83.
Martin BL, Kimelman D.
SourceDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA. AbstractFormation of the early vertebrate embryo depends on a Brachyury/Wnt autoregulatory loop within the posterior mesodermal progenitors. We show that exogenous retinoic acid (RA), which dramatically truncates the embryo, represses expression of the zebrafish brachyury ortholog no tail (ntl), causing a failure to sustain the loop. We found that Ntl functions normally to protect the autoregulatory loop from endogenous RA by directly activating cyp26a1 expression. Thus, the embryonic mesodermal progenitors uniquely establish their own niche--with Brachyury being essential for creating a domain of high Wnt and low RA signaling--rather than having a niche created by separate support cells.
Mesoderm Development - Limit Title
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