|A personal message from Dr Mark Hill (May 2020)
| I have decided to take early retirement in September 2020. During the many years online I have received wonderful feedback from many readers, researchers and students interested in human embryology. I especially thank my research collaborators and contributors to the site. The good news is Embryology will remain online and I will continue my association with UNSW Australia. I look forward to updating and including the many exciting new discoveries in Embryology!
The mesoderm forms the middle layer of the early trilaminar embryo germ layers (ectoderm, mesoderm and endoderm) formed by gastrulation. The segmentation of the initial mesoderm into somites, and their regular addition, is often used to stage embryonic development (23 somite embryo).
This middle germ layer forms connective tissues and muscle throughout the body, with the exception of in the head region where some of these structures have a neural crest (ectoderm) origin.
- connective tissues - cartilage, bone, blood, blood vessel endothelium, dermis, etc.
- muscle - cardiac, skeletal, smooth.
Students often mix-up the terms mesoderm (middle layer) with mesenchyme (embryonic connective tissue). It is true that mesoderm initially does have a mesenchymal cellular organisation, but can also form a range of epithelial structures (surrounding somites, mesothelium lining of body cavities).
Some Recent Findings
Mesenchymal cells of the developing limb bud possess long and highly dynamic cytoplasmic extensions.
- BMP and FGF signaling interact to pattern mesoderm by controlling basic helix-loop-helix transcription factor activity "The mesodermal germ layer is patterned into mediolateral subtypes by signaling factors including BMP and FGF. How these pathways are integrated to induce specific mediolateral cell fates is not well understood. We used mesoderm derived from post-gastrulation neuromesodermal progenitors (NMPs), which undergo a binary mediolateral patterning decision, as a simplified model to understand how FGF acts together with BMP to impart mediolateral fate. Using zebrafish and mouse NMPs, we identify an evolutionarily conserved mechanism of BMP and FGF mediated mediolateral mesodermal patterning that occurs through modulation of basic helix-loop-helix (bHLH) transcription factor activity. BMP imparts lateral fate through induction of Id helix loop helix (HLH) proteins, which antagonize bHLH transcription factors, induced by FGF signaling, that specify medial fate. We extend our analysis of zebrafish development to show that bHLH activity is responsible for the mediolateral patterning of the entire mesodermal germ layer."
- BRACHYURY directs histone acetylation to target loci during mesoderm development "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." blood
|These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.
See also the Discussion Page for other references listed by year and References on this current page.
- STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm migration in the mouse embryo "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." (More? cell migration | NCBI Gene - STRIP1)
- An atlas of transcriptional, chromatin accessibility, and surface marker changes in human mesoderm development "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)."
- A role for Vg1/Nodal signaling in specification of the intermediate mesoderm "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. ... We postulate that Nodal-like signaling regulates IM formation by modulating the IM-inducing effects of BMP signaling." Renal System Development
- Signaling gradients during paraxial mesoderm development "These studies indicate that high levels of Wnt and FGF signaling are required for the segmentation clock activity. Furthermore, we discuss how these signaling gradients act in a dose-dependent manner in the progenitors of the paraxial mesoderm, partly by regulating cell movements during gastrulation. Finally, links between the process of axial specification of vertebral segments and Hox gene expression are discussed."
- Transcriptional profiling of the nucleus pulposus: say yes to notochord "This editorial addresses the debate concerning the origin of adult nucleus pulposus cells in the light of profiling studies by Minogue and colleagues. In their report of several marker genes that distinguish nucleus pulposus cells from other related cell types, the authors provide novel insights into the notochordal nature of the former. Together with recently published work, their work lends support to the view that all cells present within the nucleus pulposus are derived from the notochord. Hence, the choice of an animal model for disc research should be based on considerations other than the cell loss and replacement by non-notochordal cells."
|The nested tables below show an overview of the different mesoderm-derived tissues (links go to topic pages).
|intervertebral disc nucleus pulposis
|body wall connective tissue
||gastrointestinal tract connective tissue
||gastrointestinal tract smooth muscle
||respiratory connective tissue
||villi connective tissue
||villi blood vessels
|Overview: Ectoderm | Mesoderm | Endoderm Layers: ectoderm | mesoderm | endoderm
Mesoderm Formation during Gastrulation
Human embryo (stage 10
- Links: gastrulation
Notochord secreting sonic hedgehog, shown in white
Mesoderm Regions (week 3)
- Embryo Stage 7 (dorsal)
Primitive streak and node
Oral and cloacal membranes
renal and genital
The origin of extra-embryonic mesoderm (EEM) has been extensively discussed in the literature. This mesoderm lies outside the embryo, associated with fetal membrane and placenta development. This mesoderm formed at gastrulation along with the embryonic mesoderm from the proximal side of the primitive streak. A recent study in mouse, has shown that the primitive streak absence and excessive epiblast Nodal activity in pre-gastrulation stage, but not in the primitive streak cells during gastrulation, disrupts extraembryonic mesoderm development.
- Links: placenta | placental membranes
- ↑ Sanders TA, Llagostera E & Barna M. (2013). Specialized filopodia direct long-range transport of SHH during vertebrate tissue patterning. Nature , 497, 628-32. PMID: 23624372 DOI.
- ↑ Row RH, Pegg A, Kinney B, Farr GH, Maves L, Lowell S, Wilson V & Martin BL. (2018). BMP and FGF signaling interact to pattern mesoderm by controlling basic helix-loop-helix transcription factor activity. Elife , 7, . PMID: 29877796 DOI.
- ↑ Beisaw A, Tsaytler P, Koch F, Schmitz SU, Melissari MT, Senft AD, Wittler L, Pennimpede T, Macura K, Herrmann BG & Grote P. (2018). BRACHYURY directs histone acetylation to target loci during mesoderm development. EMBO Rep. , 19, 118-134. PMID: 29141987 DOI.
- ↑ Bazzi H, Soroka E, Alcorn HL & Anderson KV. (2017). STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm migration in the mouse embryo. Proc. Natl. Acad. Sci. U.S.A. , 114, E10928-E10936. PMID: 29203676 DOI.
- ↑ Koh PW, Sinha R, Barkal AA, Morganti RM, Chen A, Weissman IL, Ang LT, Kundaje A & Loh KM. (2016). An atlas of transcriptional, chromatin accessibility, and surface marker changes in human mesoderm development. Sci Data , 3, 160109. PMID: 27996962 DOI.
- ↑ Fleming BM, Yelin R, James RG & Schultheiss TM. (2013). A role for Vg1/Nodal signaling in specification of the intermediate mesoderm. Development , 140, 1819-29. PMID: 23533180 DOI.
- ↑ Aulehla A & Pourquié O. (2010). Signaling gradients during paraxial mesoderm development. Cold Spring Harb Perspect Biol , 2, a000869. PMID: 20182616 DOI.
- ↑ Shapiro IM & Risbud MV. (2010). Transcriptional profiling of the nucleus pulposus: say yes to notochord. Arthritis Res. Ther. , 12, 117. PMID: 20497604 DOI.
- ↑ Jin JZ, Zhu Y, Warner D & Ding J. (2016). Analysis of extraembryonic mesodermal structure formation in the absence of morphological primitive streak. Dev. Growth Differ. , 58, 522-9. PMID: 27273137 DOI.
Risbud MV, Schaer TP & Shapiro IM. (2010). Toward an understanding of the role of notochordal cells in the adult intervertebral disc: from discord to accord. Dev. Dyn. , 239, 2141-8. PMID: 20568241 DOI.
Burke AC. (2007). Development and evolution of the vertebrate mesoderm. Dev. Dyn. , 236, 2369-70. PMID: 17705304 DOI.
Martin BL & Kimelman D. (2010). Brachyury establishes the embryonic mesodermal progenitor niche. Genes Dev. , 24, 2778-83. PMID: 21159819 DOI.
Korecki CL, Taboas JM, Tuan RS & Iatridis JC. (2010). Notochordal cell conditioned medium stimulates mesenchymal stem cell differentiation toward a young nucleus pulposus phenotype. Stem Cell Res Ther , 1, 18. PMID: 20565707 DOI.
Trainor PA, Tan SS & Tam PP. (1994). Cranial paraxial mesoderm: regionalisation of cell fate and impact on craniofacial development in mouse embryos. Development , 120, 2397-408. PMID: 7956820
Florian J. (1933). The Early Development of Man, with Special Reference to the Development of the Mesoderm and Cloacal Membrane. J. Anat. , 67, 263-76. PMID: 17104422
Search NLM Online Textbooks: "Mesoderm" : Developmental Biology | The Cell- A molecular Approach | Molecular Biology of the Cell | Endocrinology
Search Pubmed: Mesoderm | Notochord
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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/Mesoderm
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