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Experimental & Molecular Medicine Aug 2020Pluripotent stem cells (PSCs) are attractive regenerative therapy tools for skeletal tissues. However, a deep understanding of skeletal development is required in order... (Review)
Review
Pluripotent stem cells (PSCs) are attractive regenerative therapy tools for skeletal tissues. However, a deep understanding of skeletal development is required in order to model this development with PSCs, and for the application of PSCs in clinical settings. Skeletal tissues originate from three types of cell populations: the paraxial mesoderm, lateral plate mesoderm, and neural crest. The paraxial mesoderm gives rise to the sclerotome mainly through somitogenesis. In this process, key developmental processes, including initiation of the segmentation clock, formation of the determination front, and the mesenchymal-epithelial transition, are sequentially coordinated. The sclerotome further forms vertebral columns and contributes to various other tissues, such as tendons, vessels (including the dorsal aorta), and even meninges. To understand the molecular mechanisms underlying these developmental processes, extensive studies have been conducted. These studies have demonstrated that a gradient of activities involving multiple signaling pathways specify the embryonic axis and induce cell-type-specific master transcription factors in a spatiotemporal manner. Moreover, applying the knowledge of mesoderm development, researchers have attempted to recapitulate the in vivo development processes in in vitro settings, using mouse and human PSCs. In this review, we summarize the state-of-the-art understanding of mesoderm development and in vitro modeling of mesoderm development using PSCs. We also discuss future perspectives on the use of PSCs to generate skeletal tissues for basic research and clinical applications.
Topics: Animals; Bone Development; Bone and Bones; Humans; Mesoderm; Pluripotent Stem Cells; Somites; Wound Healing
PubMed: 32788657
DOI: 10.1038/s12276-020-0482-1 -
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 -
The International Journal of... 2017The vertebrate head characteristically exhibits a complex pattern with sense organs, brain, paired eyes and jaw muscles, and the brain case is not found in other... (Review)
Review
The vertebrate head characteristically exhibits a complex pattern with sense organs, brain, paired eyes and jaw muscles, and the brain case is not found in other chordates. How the extant vertebrate head has evolved remains enigmatic. Historically, there have been two conflicting views on the origin of the vertebrate head, segmental and non-segmental views. According to the segmentalists, the vertebrate head is organized as a metameric structure composed of segments equivalent to those in the trunk; a metamere in the vertebrate head was assumed to consist of a somite, a branchial arch and a set of cranial nerves, considering that the head evolved from rostral segments of amphioxus-like ancestral vertebrates. Non-segmentalists, however, considered that the vertebrate head was not segmental. In that case, the ancestral state of the vertebrate head may be non-segmented, and rostral segments in amphioxus might have been secondarily gained, or extant vertebrates might have evolved through radical modifications of amphioxus-like ancestral vertebrate head. Comparative studies of mesodermal development in amphioxus and vertebrate gastrula embryos have revealed that mesodermal gene expressions become segregated into two domains anteroposteriorly to specify the head mesoderm and trunk mesoderm only in vertebrates; in this segregation, key genes such as delta and hairy, involved in segment formation, are expressed in the trunk mesoderm, but not in the head mesoderm, strongly suggesting that the head mesoderm of extant vertebrates is not segmented. Taken together, the above finding possibly adds a new insight into the origin of the vertebrate head; the vertebrate head mesoderm would have evolved through an anteroposterior polarization of the paraxial mesoderm if the ancestral vertebrate had been amphioxus-like.
Topics: Animals; Body Patterning; Cephalochordata; Gene Expression Regulation, Developmental; Head; Lancelets; Models, Biological; Somites; Vertebrates
PubMed: 29319111
DOI: 10.1387/ijdb.170121to -
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 -
Circulation Research Jan 2015The heart is the first organ to form during embryonic development. Given the complex nature of cardiac differentiation and morphogenesis, it is not surprising that some... (Review)
Review
The heart is the first organ to form during embryonic development. Given the complex nature of cardiac differentiation and morphogenesis, it is not surprising that some form of congenital heart disease is present in ≈1 percent of newborns. The molecular determinants of heart development have received much attention over the past several decades. This has been driven in large part by an interest in understanding the causes of congenital heart disease coupled with the potential of using knowledge from developmental biology to generate functional cells and tissues that could be used for regenerative medicine purposes. In this review, we highlight the critical signaling pathways and transcription factor networks that regulate cardiomyocyte lineage specification in both in vivo and in vitro models. Special focus will be given to epigenetic regulators that drive the commitment of cardiomyogenic cells from nascent mesoderm and their differentiation into chamber-specific myocytes, as well as regulation of myocardial trabeculation.
Topics: Animals; Cell Differentiation; Cell Lineage; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Humans; Mesoderm; Myocardium; Myocytes, Cardiac; Signal Transduction
PubMed: 25593278
DOI: 10.1161/CIRCRESAHA.116.302752 -
Current Topics in Developmental Biology 2015The tongue and mandible have common origins. They arise simultaneously from the mandibular arch and are coordinated in their development and growth, which is evident... (Review)
Review
The tongue and mandible have common origins. They arise simultaneously from the mandibular arch and are coordinated in their development and growth, which is evident from several clinical conditions such as Pierre Robin sequence. Here, we review in detail the molecular networks controlling both mandible and tongue development. We also discuss their mechanical relationship and evolution as well as the potential for stem cell-based therapies for disorders affecting these organs.
Topics: Animals; Gene Expression Regulation, Developmental; Humans; Mandible; Mesoderm; Neural Crest; Osteogenesis; Stem Cells; Tendons; Tongue
PubMed: 26589920
DOI: 10.1016/bs.ctdb.2015.07.023 -
Nature Communications Aug 2020Visceral organs, such as the lungs, stomach and liver, are derived from the fetal foregut through a series of inductive interactions between the definitive endoderm (DE)...
Visceral organs, such as the lungs, stomach and liver, are derived from the fetal foregut through a series of inductive interactions between the definitive endoderm (DE) and the surrounding splanchnic mesoderm (SM). While DE patterning is fairly well studied, the paracrine signaling controlling SM regionalization and how this is coordinated with epithelial identity is obscure. Here, we use single cell transcriptomics to generate a high-resolution cell state map of the embryonic mouse foregut. This identifies a diversity of SM cell types that develop in close register with the organ-specific epithelium. We infer a spatiotemporal signaling network of endoderm-mesoderm interactions that orchestrate foregut organogenesis. We validate key predictions with mouse genetics, showing the importance of endoderm-derived signals in mesoderm patterning. Finally, leveraging these signaling interactions, we generate different SM subtypes from human pluripotent stem cells (hPSCs), which previously have been elusive. The single cell data can be explored at: https://research.cchmc.org/ZornLab-singlecell .
Topics: Animals; Cell Lineage; Digestive System; Endoderm; Gene Expression Profiling; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Humans; Internet; Mesoderm; Mice, Inbred C57BL; Organogenesis; Signal Transduction; Single-Cell Analysis; Transcription Factors
PubMed: 32855417
DOI: 10.1038/s41467-020-17968-x -
Seminars in Cell & Developmental Biology Dec 2017Pluripotent stem cells represent important tools for both basic and translational science as they enable to study mechanisms of development, model diseases in vitro and... (Review)
Review
Pluripotent stem cells represent important tools for both basic and translational science as they enable to study mechanisms of development, model diseases in vitro and provide a potential source of tissue-specific progenitors for cell therapy. Concomitantly with the increasing knowledge of the molecular mechanisms behind activation of the skeletal myogenic program during embryonic development, novel findings in the stem cell field provided the opportunity to begin recapitulating in vitro the events occurring during specification of the myogenic lineage. In this review, we will provide a perspective of the molecular mechanisms responsible for skeletal myogenic commitment in the embryo and how this knowledge was instrumental for specifying this lineage from pluripotent stem cells. In addition, we will discuss the current limitations for properly recapitulating skeletal myogenesis in the petri dish, and we will provide insights about future applications of pluripotent stem cell-derived myogenic cells.
Topics: Animals; Cell Differentiation; Cell Lineage; Gene Expression Regulation, Developmental; Humans; Mesoderm; Muscle Development; Muscle Proteins; Muscle, Skeletal; Pluripotent Stem Cells
PubMed: 29107681
DOI: 10.1016/j.semcdb.2017.10.031 -
FEBS Letters Dec 2019The haematopoietic system is established during embryonic life through a series of developmental steps that culminates with the generation of haematopoietic stem cells.... (Review)
Review
The haematopoietic system is established during embryonic life through a series of developmental steps that culminates with the generation of haematopoietic stem cells. Characterisation of the transcriptional network that regulates blood cell emergence has led to the identification of transcription factors essential for this process. Among the many factors wired within this complex regulatory network, ETV2, SCL and RUNX1 are the central components. All three factors are absolutely required for blood cell generation, each one controlling a precise step of specification from the mesoderm germ layer to fully functional blood progenitors. Insight into the transcriptional control of blood cell emergence has been used for devising protocols to generate blood cells de novo, either through reprogramming of somatic cells or through forward programming of pluripotent stem cells. Interestingly, the physiological process of blood cell generation and its laboratory-engineered counterpart have very little in common.
Topics: Blood Cells; Cell Differentiation; Cellular Reprogramming; Core Binding Factor Alpha 2 Subunit; Hematopoietic Stem Cells; Humans; Mesoderm; Pluripotent Stem Cells; T-Cell Acute Lymphocytic Leukemia Protein 1; Transcription Factors; Transcriptional Activation
PubMed: 31432499
DOI: 10.1002/1873-3468.13585 -
Developmental Dynamics : An Official... Mar 2016Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly... (Review)
Review
Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans.
Topics: Animals; Embryo, Mammalian; Epithelium; Humans; Mesoderm; Organogenesis; Signal Transduction; Viscera
PubMed: 26638186
DOI: 10.1002/dvdy.24373