Authors: Kyle M Loh, Angela Chen, Pang Wei Koh...

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

Review

Authors: Benjamin L Martin

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

Authors: Danelle Devenport

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

Review

Authors: Karin D Prummel, Susan Nieuwenhuize, Christian Mosimann...

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

Review

Authors: Elisabetta Ferretti, Anna-Katerina Hadjantonakis

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

Authors: Min Zhu, Bin Gu, Evan C Thomas...

Physical processes ultimately shape tissue during development. Two emerging proposals are that cells migrate toward stiffer tissue (durotaxis) and that the extent of cell rearrangements reflects tissue phase, but it is unclear whether and how these concepts are related. Here, we identify fibronectin-dependent tissue stiffness as a control variable that underlies and unifies these phenomena in vivo. In murine limb bud mesoderm, cells are either caged, move directionally, or intercalate as a function of their location along a stiffness gradient. A modified Landau phase equation that incorporates tissue stiffness accurately predicts cell diffusivity upon loss or gain of fibronectin. Fibronectin is regulated by WNT5A-YAP feedback that controls cell movements, tissue shape, and skeletal pattern. The results identify a key determinant of phase transition and show how fibronectin-dependent directional cell movement emerges in a mixed-phase environment in vivo.

Topics: Fibronectins; Animals; Mesoderm; Mice; Cell Movement; Wnt-5a Protein

PubMed: 39028807
DOI: 10.1126/sciadv.adl6366

Review

Authors: Yuchuan Miao, Olivier Pourquié

Segmentation is a fundamental feature of the vertebrate body plan. This metameric organization is first implemented by somitogenesis in the early embryo, when paired epithelial blocks called somites are rhythmically formed to flank the neural tube. Recent advances in in vitro models have offered new opportunities to elucidate the mechanisms that underlie somitogenesis. Notably, models derived from human pluripotent stem cells introduced an efficient proxy for studying this process during human development. In this Review, we summarize the current understanding of somitogenesis gained from both in vivo studies and in vitro studies. We deconstruct the spatiotemporal dynamics of somitogenesis into four distinct modules: dynamic events in the presomitic mesoderm, segmental determination, somite anteroposterior polarity patterning, and epithelial morphogenesis. We first focus on the segmentation clock, as well as signalling and metabolic gradients along the tissue, before discussing the clock and wavefront and other models that account for segmental determination. We then detail the molecular and cellular mechanisms of anteroposterior polarity patterning and somite epithelialization.

Topics: Somites; Animals; Humans; Body Patterning; Vertebrates; Gene Expression Regulation, Developmental; Embryonic Development; Mesoderm; Signal Transduction; Morphogenesis

PubMed: 38418851
DOI: 10.1038/s41580-024-00709-z

Review

Authors: Shi Wei, Qiang Wang

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

Review

Authors: Drew M Noden, Paul A Trainor

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

Review

Authors: Ann Sutherland, Raymond Keller, Alyssa Lesko...

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