-
Development (Cambridge, England) Dec 1998Paraxial Protocadherin (PAPC) encodes a transmembrane protein expressed initially in Spemann's organizer and then in paraxial mesoderm. Together with another member of...
Paraxial Protocadherin (PAPC) encodes a transmembrane protein expressed initially in Spemann's organizer and then in paraxial mesoderm. Together with another member of the protocadherin family, Axial Protocadherin (AXPC), it subdivides gastrulating mesoderm into paraxial and axial domains. PAPC has potent homotypic cell adhesion activity in cell dissociation and reaggregation assays. Gain- and loss-of-function microinjection studies indicate that PAPC plays an important role in the convergence and extension movements that drive Xenopus gastrulation. Thus, PAPC is not only an adhesion molecule but also a component of the machinery that drives gastrulation movements in Xenopus. PAPC may provide a link between regulatory genes in Spemann's organizer and the execution of cell behaviors during morphogenesis.
Topics: Amino Acid Sequence; Animals; Body Patterning; Cadherins; Cell Adhesion; Cell Aggregation; Cell Movement; DNA, Complementary; Embryo, Nonmammalian; Gastrula; Mesoderm; Molecular Sequence Data; Notochord; Organ Culture Techniques; Protocadherins; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic; Xenopus; Xenopus Proteins
PubMed: 9806917
DOI: 10.1242/dev.125.23.4681 -
Developmental Biology Jun 2009The eye field is initially a large single domain at the anterior end of the neural plate and is the first indication of optic potential in the vertebrate embryo. During...
The eye field is initially a large single domain at the anterior end of the neural plate and is the first indication of optic potential in the vertebrate embryo. During the course of development, this domain is subject to interactions that shape and refine the organogenic field. The action of the prechordal mesoderm in bisecting this single region into two bilateral domains has been well described, however the role of signalling interactions in the further restriction and refinement of this domain has not been previously characterised. Here we describe a role for the rostral cephalic paraxial mesoderm in limiting the extent of the eye field. The anterior transposition of this mesoderm or its ablation disrupted normal development of the eye. Importantly, perturbation of optic vesicle development occurred in the absence of any detectable changes in the pattern of neighbouring regions of the neural tube. Furthermore, negative regulation of eye development is a property unique to the rostral paraxial mesoderm. The rostral paraxial mesoderm expresses members of the bone morphogenetic protein (BMP) family of signalling molecules and manipulation of endogenous BMP signalling resulted in abnormalities of the early optic primordia.
Topics: Animals; Bone Morphogenetic Proteins; Chick Embryo; Coturnix; Electroporation; Eye; In Situ Hybridization; Mesoderm; Recombinant Proteins
PubMed: 19362544
DOI: 10.1016/j.ydbio.2009.04.008 -
Developmental Biology Feb 2014During organogenesis, Sonic hedgehog (Shh) possesses dual functions: Shh emanating from midline structures regulates the positioning of bilateral structures at early...
During organogenesis, Sonic hedgehog (Shh) possesses dual functions: Shh emanating from midline structures regulates the positioning of bilateral structures at early stages, whereas organ-specific Shh locally regulates organ morphogenesis at later stages. The mesonephros is a transient embryonic kidney in amniote, whereas it becomes definitive adult kidney in some anamniotes. Thus, elucidating the regulation of mesonephros formation has important implications for our understanding of kidney development and evolution. In Shh knockout (KO) mutant mice, the mesonephros was displaced towards the midline and ectopic mesonephric tubules (MTs) were present in the caudal mesonephros. Mesonephros-specific ablation of Shh in Hoxb7-Cre;Shh(flox/-) and Sall1(CreERT2/+);Shh(flox/-) mice embryos indicated that Shh expressed in the mesonephros was not required for either the development of the mesonephros or the differentiation of the male reproductive tract. Moreover, stage-specific ablation of Shh in Shh(CreERT2/flox) mice showed that notochord- and/or floor plate-derived Shh were essential for the regulation of the number and position of MTs. Lineage analysis of hedgehog (Hh)-responsive cells, and analysis of gene expression in Shh KO embryos suggested that Shh regulated nephrogenic gene expression indirectly, possibly through effects on the paraxial mesoderm. These data demonstrate the essential role of midline-derived Shh in local tissue morphogenesis and differentiation.
Topics: Animals; Cell Differentiation; Cell Lineage; Crosses, Genetic; Female; Forkhead Transcription Factors; Gene Expression Regulation, Developmental; Hedgehog Proteins; In Situ Hybridization; Kidney; Male; Mesoderm; Mesonephros; Mice; Mice, Inbred ICR; Mice, Knockout; Notochord
PubMed: 24370450
DOI: 10.1016/j.ydbio.2013.12.026 -
Development (Cambridge, England) Sep 2018Head and trunk muscles have discrete embryological origins and are governed by distinct regulatory programmes. Whereas the developmental route of trunk muscles from...
Head and trunk muscles have discrete embryological origins and are governed by distinct regulatory programmes. Whereas the developmental route of trunk muscles from mesoderm is well studied, that of head muscles is ill defined. Here, we show that, unlike the myogenic trunk paraxial mesoderm, head mesoderm development is independent of the T/Tbx6 network in mouse. We reveal that, in contrast to Wnt and FGF-driven trunk mesoderm, dual inhibition of Wnt/β-catenin and Nodal specifies head mesoderm. Remarkably, the progenitors derived from embryonic stem cells by dual inhibition efficiently differentiate into cardiac and skeletal muscle cells. This twin potential is the defining feature of cardiopharyngeal mesoderm: the head subtype giving rise to heart and branchiomeric head muscles. Therefore, our findings provide compelling evidence that dual inhibition specifies head mesoderm and unravel the mechanism that diversifies head and trunk muscle programmes during early mesoderm fate commitment. Significantly, this is the first report of directed differentiation of pluripotent stem cells, without transgenes, into progenitors with muscle/heart dual potential. Ability to generate branchiomeric muscle could catalyse efforts in modelling myopathies that selectively involve head muscles.
Topics: Animals; Cell Differentiation; Cells, Cultured; Head; Mesoderm; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Muscle, Skeletal; Nodal Protein; Pluripotent Stem Cells; T-Box Domain Proteins; Transcription Factors; Wnt Proteins; beta Catenin
PubMed: 30237317
DOI: 10.1242/dev.160945 -
Development (Cambridge, England) Nov 2014Neuromesodermal (NM) stem cells generate neural and paraxial presomitic mesoderm (PSM) cells, which are the respective progenitors of the spinal cord and musculoskeleton...
Neuromesodermal (NM) stem cells generate neural and paraxial presomitic mesoderm (PSM) cells, which are the respective progenitors of the spinal cord and musculoskeleton of the trunk and tail. The Wnt-regulated basic helix-loop-helix (bHLH) transcription factor mesogenin 1 (Msgn1) has been implicated as a cooperative regulator working in concert with T-box genes to control PSM formation in zebrafish, although the mechanism is unknown. We show here that, in mice, Msgn1 alone controls PSM differentiation by directly activating the transcriptional programs that define PSM identity, epithelial-mesenchymal transition, motility and segmentation. Forced expression of Msgn1 in NM stem cells in vivo reduced the contribution of their progeny to the neural tube, and dramatically expanded the unsegmented mesenchymal PSM while blocking somitogenesis and notochord differentiation. Expression of Msgn1 was sufficient to partially rescue PSM differentiation in Wnt3a(-/-) embryos, demonstrating that Msgn1 functions downstream of Wnt3a as the master regulator of PSM differentiation. Our data provide new insights into how cell fate decisions are imposed by the expression of a single transcriptional regulator.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Chromatin Immunoprecipitation; Electrophoretic Mobility Shift Assay; Flow Cytometry; Gene Expression Profiling; Gene Expression Regulation, Developmental; Immunohistochemistry; In Situ Hybridization; Luciferases; Mesoderm; Mice; Mice, Knockout; Microarray Analysis; Muscle, Skeletal; Nervous System; Reverse Transcriptase Polymerase Chain Reaction; Wnt3A Protein
PubMed: 25371364
DOI: 10.1242/dev.110908 -
Science Advances Jan 2024Spatiotemporal patterns widely occur in biological, chemical, and physical systems. Particularly, embryonic development displays a diverse gamut of repetitive patterns... (Review)
Review
Spatiotemporal patterns widely occur in biological, chemical, and physical systems. Particularly, embryonic development displays a diverse gamut of repetitive patterns established in many tissues and organs. Branching treelike structures in lungs, kidneys, livers, pancreases, and mammary glands as well as digits and bones in appendages, teeth, and palates are just a few examples. A fascinating instance of repetitive patterning is the sequential segmentation of the primary body axis, which is conserved in all vertebrates and many arthropods and annelids. In these species, the body axis elongates at the posterior end of the embryo containing an unsegmented tissue. Meanwhile, segments sequentially bud off from the anterior end of the unsegmented tissue, laying down an exquisite repetitive pattern and creating a segmented body plan. In vertebrates, the paraxial mesoderm is sequentially divided into somites. In this review, we will discuss the most prominent models, the most puzzling experimental data, and outstanding questions in vertebrate somite segmentation.
Topics: Animals; Body Patterning; Somites; Mesoderm; Vertebrates; Embryonic Development; Gene Expression Regulation, Developmental
PubMed: 38277458
DOI: 10.1126/sciadv.adk8937 -
Cell Stem Cell Nov 2020Brown adipocytes (BAs) are a potential cell source for the treatment of metabolic disease, including type 2 diabetes. In this report, human pluripotent stem cells...
Brown adipocytes (BAs) are a potential cell source for the treatment of metabolic disease, including type 2 diabetes. In this report, human pluripotent stem cells (hPSCs) are subject to directed differentiation through a paraxial mesoderm progenitor state that generates BAs at high efficiency. Molecular analysis identifies potential regulatory networks for BA development, giving insight into development along this lineage. hPSC-derived BAs undergo elevated rates of glycolysis, uncoupled respiration, and lipolysis that are responsive to changes in cyclic AMP (cAMP)-dependent signaling, consistent with metabolic activity in BA tissue depots. Transplanted human BAs engraft into the inter-scapular region of recipient mice and exhibit thermogenic activity. Recipient animals have elevated metabolic activity, respiratory exchange ratios, and whole-body energy expenditure. Finally, transplanted BAs reduce circulating glucose levels in hyperglycemic animals. These data provide a roadmap for brown adipocyte development and indicate that BAs generated from hPSCs have potential as a tool for therapeutic development.
Topics: Adipocytes, Brown; Animals; Cell Differentiation; Diabetes Mellitus, Type 2; Humans; Mesoderm; Mice; Pluripotent Stem Cells; Thermogenesis
PubMed: 32783886
DOI: 10.1016/j.stem.2020.07.013 -
Seminars in Cell & Developmental Biology Jul 2022Human pluripotent stem cells can differentiate into any cell type given appropriate signals and hence have been used to research early human development of many tissues... (Review)
Review
Human pluripotent stem cells can differentiate into any cell type given appropriate signals and hence have been used to research early human development of many tissues and diseases. Here, we review the major biological factors that regulate cartilage and bone development through the three main routes of neural crest, lateral plate mesoderm and paraxial mesoderm. We examine how these routes have been used in differentiation protocols that replicate skeletal development using human pluripotent stem cells and how these methods have been refined and improved over time. Finally, we discuss how pluripotent stem cells can be employed to understand human skeletal genetic diseases with a developmental origin and phenotype, and how developmental protocols have been applied to gain a better understanding of these conditions.
Topics: Bone and Bones; Cartilage; Cell Differentiation; Humans; Mesoderm; Neural Crest; Pluripotent Stem Cells
PubMed: 34949507
DOI: 10.1016/j.semcdb.2021.11.024 -
Development (Cambridge, England) Sep 2015Neuromesodermal progenitors (NMps) contribute to both the elongating spinal cord and the adjacent paraxial mesoderm. It has been assumed that these cells arise as a... (Review)
Review
Neuromesodermal progenitors (NMps) contribute to both the elongating spinal cord and the adjacent paraxial mesoderm. It has been assumed that these cells arise as a result of patterning of the anterior neural plate. However, as the molecular mechanisms that specify NMps in vivo are uncovered, and as protocols for generating these bipotent cells from mouse and human pluripotent stem cells in vitro are established, the emerging data suggest that this view needs to be revised. Here, we review the characteristics, regulation, in vitro derivation and in vivo induction of NMps. We propose that these cells arise within primitive streak-associated epiblast via a mechanism that is separable from that which establishes neural fate in the anterior epiblast. We thus argue for the existence of two distinct routes for making central nervous system progenitors.
Topics: Animals; Body Patterning; Embryo, Mammalian; Humans; Mesoderm; Neural Stem Cells; Signal Transduction; Spinal Cord; Stem Cells
PubMed: 26329597
DOI: 10.1242/dev.119768 -
BMC Developmental Biology Jun 2008Co-ordinated cell movement is a fundamental feature of developing embryos. Massive cell movements occur during vertebrate gastrulation and during the subsequent...
BACKGROUND
Co-ordinated cell movement is a fundamental feature of developing embryos. Massive cell movements occur during vertebrate gastrulation and during the subsequent extension of the embryonic body axis. These are controlled by cell-cell signalling and a number of pathways have been implicated. Here we use long-term video microscopy in chicken embryos to visualize the migration routes and movement behaviour of mesoderm progenitor cells as they emerge from the primitive streak (PS) between HH stages 7 and 10.
RESULTS
We observed distinct cell movement behaviours along the length of the streak and determined that this is position dependent with cells responding to environmental cues. The behaviour of cells was altered by exposing embryos or primitive streak explants to cell pellets expressing Wnt3a and Wnt5a, without affecting cell fates, thus implicating these ligands in the regulation of cell movement behaviour. Interestingly younger embryos were not responsive, suggesting that Wnt3a and Wnt5a are specifically involved in the generation of posterior mesoderm, consistent with existing mouse and zebrafish mutants. To investigate which downstream components are involved mutant forms of dishevelled (dsh) and prickle1 (pk1) were electroporated into the primitive streak. These had differential effects on the behaviour of mesoderm progenitors emerging from anterior or posterior regions of the streak, suggesting that multiple Wnt pathways are involved in controlling cell migration during extension of the body axis in amniote embryos.
CONCLUSION
We suggest that the distinct behaviours of paraxial and lateral mesoderm precursors are regulated by the opposing actions of Wnt5a and Wnt3a as they leave the primitive streak in neurula stage embryos. Our data suggests that Wnt5a acts via prickle to cause migration of cells from the posterior streak. In the anterior streak, this is antagonised by Wnt3a to generate non-migratory medial mesoderm.
Topics: Animals; Body Patterning; Cell Movement; Chick Embryo; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Mesoderm; Morphogenesis; Primitive Streak; Signal Transduction; Time Factors; Wnt Proteins
PubMed: 18541012
DOI: 10.1186/1471-213X-8-63