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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 -
Cell Jul 2016Stem-cell differentiation to desired lineages requires navigating alternating developmental paths that often lead to unwanted cell types. Hence, comprehensive...
Stem-cell differentiation to desired lineages requires navigating alternating developmental paths that often lead to unwanted cell types. Hence, comprehensive developmental roadmaps are crucial to channel stem-cell differentiation toward desired fates. To this end, here, we map bifurcating lineage choices leading from pluripotency to 12 human mesodermal lineages, including bone, muscle, and heart. We defined the extrinsic signals controlling each binary lineage decision, enabling us to logically block differentiation toward unwanted fates and rapidly steer pluripotent stem cells toward 80%-99% pure human mesodermal lineages at most branchpoints. This strategy enabled the generation of human bone and heart progenitors that could engraft in respective in vivo models. Mapping stepwise chromatin and single-cell gene expression changes in mesoderm development uncovered somite segmentation, a previously unobservable human embryonic event transiently marked by HOPX expression. Collectively, this roadmap enables navigation of mesodermal development to produce transplantable human tissue progenitors and uncover developmental processes. VIDEO ABSTRACT.
Topics: Bone Morphogenetic Proteins; Bone and Bones; Heart; Homeodomain Proteins; Humans; Mesoderm; Myocytes, Cardiac; Pluripotent Stem Cells; Primitive Streak; Signal Transduction; Single-Cell Analysis; Somites; Stem Cells; Tumor Suppressor Proteins; Wnt Proteins
PubMed: 27419872
DOI: 10.1016/j.cell.2016.06.011 -
Development (Cambridge, England) Jun 2020The lateral plate mesoderm (LPM) forms the progenitor cells that constitute the heart and cardiovascular system, blood, kidneys, smooth muscle lineage and limb skeleton... (Review)
Review
The lateral plate mesoderm (LPM) forms the progenitor cells that constitute the heart and cardiovascular system, blood, kidneys, smooth muscle lineage and limb skeleton in the developing vertebrate embryo. Despite this central role in development and evolution, the LPM remains challenging to study and to delineate, owing to its lineage complexity and lack of a concise genetic definition. Here, we outline the processes that govern LPM specification, organization, its cell fates and the inferred evolutionary trajectories of LPM-derived tissues. Finally, we discuss the development of seemingly disparate organ systems that share a common LPM origin.
Topics: Animals; Cardiovascular System; Cell Differentiation; Cell Lineage; Embryonic Development; Gene Expression Regulation, Developmental; Humans; Mesoderm; Stem Cells; Transcription Factors
PubMed: 32561665
DOI: 10.1242/dev.175059 -
ELife Jun 2022Advanced imaging techniques reveal details of the interactions between the two layers of the embryonic midgut that influence its ultimate shape.
Advanced imaging techniques reveal details of the interactions between the two layers of the embryonic midgut that influence its ultimate shape.
Topics: Animals; Drosophila; Endoderm; Gene Expression Regulation, Developmental; Mesoderm; Morphogenesis
PubMed: 35771125
DOI: 10.7554/eLife.80416 -
Current Opinion in Cell Biology Dec 2019The three germ layers - mesoderm, endoderm and ectoderm - constituting the cellular blueprint for the tissues and organs that will form during embryonic development, are... (Review)
Review
The three germ layers - mesoderm, endoderm and ectoderm - constituting the cellular blueprint for the tissues and organs that will form during embryonic development, are specified at gastrulation. Cells of mesodermal origin are the most abundant in the human body, representing a great variety of cell types, including the musculoskeletal system (bone, cartilage and muscle), cardiovascular system (heart, blood and blood vessels), as well as the connective tissues found throughout our bodies. A long-standing question pertains how this panoply of mesodermal cell types arises in a stereotypical fashion in time and space. This review discusses the events associated with mesoderm specification, highlighting the reconstruction of putative developmental trajectories facilitated by recent single-cell 'omic' data. We will also discuss the potential of emergent organoid systems to emulate and interrogate the dynamics of lineage specification at cellular resolution.
Topics: Animals; Cell Differentiation; Cell Lineage; Ectoderm; Embryonic Development; Endoderm; Gastrulation; Humans; Mesoderm
PubMed: 31476530
DOI: 10.1016/j.ceb.2019.07.012 -
The Journal of Biological Chemistry Jun 2017Critical steps in the specification of embryonic cell lineages occur after implantation, but gaining insight into the molecular details of these cellular processes has... (Review)
Review
Critical steps in the specification of embryonic cell lineages occur after implantation, but gaining insight into the molecular details of these cellular processes has been challenging. Jin and co-workers now report the transcriptomic signatures and molecular heterogeneity of more than 600 single cells from mouse embryos at days 5.5 and 6.5, advancing our understanding of how early embryonic cells make cell-fate decisions into mesoderm and endoderm lineages.
Topics: Animals; Cell Lineage; Embryo, Mammalian; Endoderm; Mesoderm; Mice
PubMed: 28600307
DOI: 10.1074/jbc.H117.780585 -
Seminars in Cell & Developmental Biology Apr 2020Convergent extension is a fundamental morphogenetic process that underlies not only the generation of the elongated vertebrate body plan from the initially radially... (Review)
Review
Convergent extension is a fundamental morphogenetic process that underlies not only the generation of the elongated vertebrate body plan from the initially radially symmetrical embryo, but also the specific shape changes characteristic of many individual tissues. These tissue shape changes are the result of specific cell behaviors, coordinated in time and space, and affected by the physical properties of the tissue. While mediolateral cell intercalation is the classic cellular mechanism for producing tissue convergence and extension, other cell behaviors can also provide similar tissue-scale distortions or can modulate the effects of mediolateral cell intercalation to sculpt a specific shape. Regulation of regional tissue morphogenesis through planar polarization of the variety of underlying cell behaviors is well-recognized, but as yet is not well understood at the molecular level. Here, we review recent advances in understanding the cellular basis for convergence and extension and its regulation.
Topics: Animals; Embryo, Mammalian; Mesoderm; Morphogenesis
PubMed: 31734039
DOI: 10.1016/j.semcdb.2019.11.002 -
Neuro-mesodermal assembloids recapitulate aspects of peripheral nervous system development in vitro.Stem Cell Reports May 2023Here we describe a novel neuro-mesodermal assembloid model that recapitulates aspects of peripheral nervous system (PNS) development such as neural crest cell (NCC)...
Here we describe a novel neuro-mesodermal assembloid model that recapitulates aspects of peripheral nervous system (PNS) development such as neural crest cell (NCC) induction, migration, and sensory as well as sympathetic ganglion formation. The ganglia send projections to the mesodermal as well as neural compartment. Axons in the mesodermal part are associated with Schwann cells. In addition, peripheral ganglia and nerve fibers interact with a co-developing vascular plexus, forming a neurovascular niche. Finally, developing sensory ganglia show response to capsaicin indicating their functionality. The presented assembloid model could help to uncover mechanisms of human NCC induction, delamination, migration, and PNS development. Moreover, the model could be used for toxicity screenings or drug testing. The co-development of mesodermal and neuroectodermal tissues and a vascular plexus along with a PNS allows us to investigate the crosstalk between neuroectoderm and mesoderm and between peripheral neurons/neuroblasts and endothelial cells.
Topics: Humans; Endothelial Cells; Neural Stem Cells; Schwann Cells; Axons; Mesoderm; Neural Crest
PubMed: 37084722
DOI: 10.1016/j.stemcr.2023.03.012 -
Journal of Anatomy Nov 2005The embryonic head is populated by two robust mesenchymal populations, paraxial mesoderm and neural crest cells. Although the developmental histories of each are... (Review)
Review
The embryonic head is populated by two robust mesenchymal populations, paraxial mesoderm and neural crest cells. Although the developmental histories of each are distinct and separate, they quickly establish intimate relations that are variably important for the histogenesis and morphogenesis of musculoskeletal components of the calvaria, midface and branchial regions. This review will focus first on the genesis and organization within nascent mesodermal and crest populations, emphasizing interactions that probably initiate or augment the establishment of lineages within each. The principal goal is an analysis of the interactions between crest and mesoderm populations, from their first contacts through their concerted movements into peripheral domains, particularly the branchial arches, and continuing to stages at which both the differentiation and the integrated three-dimensional assembly of vascular, connective and muscular tissues is evident. Current views on unresolved or contentious issues, including the relevance of head somitomeres, the processes by which crest cells change locations and constancy of cell-cell relations at the crest-mesoderm interface, are addressed.
Topics: Animals; Branchial Region; Cell Communication; Cell Lineage; Embryonic Induction; Head; Mesoderm; Morphogenesis; Neural Crest
PubMed: 16313393
DOI: 10.1111/j.1469-7580.2005.00473.x -
Acta Biochimica Et Biophysica Sinica Jan 2018One of the most important events during vertebrate embryogenesis is the formation or specification of the three germ layers, endoderm, mesoderm, and ectoderm. After a... (Review)
Review
One of the most important events during vertebrate embryogenesis is the formation or specification of the three germ layers, endoderm, mesoderm, and ectoderm. After a series of rapid cleavages, embryos form the mesendoderm and ectoderm during late blastulation and early gastrulation. The mesendoderm then further differentiates into the mesoderm and endoderm. Nodal, a member of the transforming growth factor β (TGF-β) superfamily, plays a pivotal role in mesendoderm formation by regulating the expression of a number of critical transcription factors, including Mix-like, GATA, Sox, and Fox. Because the Nodal signal transduction pathway is well-characterized, increasing effort has been made to delineate the spatiotemporal modulation of Nodal signaling during embryonic development. In this review, we summarize the recent progress delineating molecular regulation of Nodal signal intensity and duration during mesendoderm formation.
Topics: Animals; Ectoderm; Endoderm; Gene Expression Regulation, Developmental; Mesoderm; Mice; Models, Genetic; Nodal Protein; Signal Transduction
PubMed: 29206913
DOI: 10.1093/abbs/gmx128