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Developmental Dynamics : An Official... May 2011During vertebrate limb development, various molecules are expressed in the presumptive limb field or the limb bud in a spatiotemporal-specific manner. The combination of... (Review)
Review
During vertebrate limb development, various molecules are expressed in the presumptive limb field or the limb bud in a spatiotemporal-specific manner. The combination of these molecules regulates cellular properties that affect limb initiation and its morphogenesis, especially cartilage formation. Cell adhesiveness of the limb mesenchyme is a key factor in the regulation of cell distribution. Differential adhesiveness of mesenchymal cells is first observed between cells in the presumptive limb field and flank region, and the adhesiveness of the cells in the limb field is higher than that of cells in the flank region. In the limb bud, the adhesiveness of mesenchymal cells shows spatiotemporal difference, which reflects the positional identity of the cells. Position-dependent cell adhesiveness is also observed in blastema cells of the regenerating limb. Therefore, local changes in cell adhesiveness are observed during limb development and regeneration, suggesting significant roles for cell adhesiveness in limb morphogenesis.
Topics: Animals; Cell Adhesion; Cell Movement; Extremities; Limb Buds; Mesoderm; Morphogenesis; Regeneration; Vertebrates
PubMed: 21290476
DOI: 10.1002/dvdy.22552 -
Cell and Tissue Research Jan 2012Recent evidence has demonstrated that endothelial cells can have a remarkable plasticity. By a process called Endothelial-to-Mesenchymal Transition (EndMT) endothelial... (Review)
Review
Recent evidence has demonstrated that endothelial cells can have a remarkable plasticity. By a process called Endothelial-to-Mesenchymal Transition (EndMT) endothelial cells convert to a more mesenchymal cell type that can give rise to cells such as fibroblasts, but also bone cells. EndMT is essential during embryonic development and tissue regeneration. Interestingly, it also plays a role in pathological conditions like fibrosis of organs such as the heart and kidney. In addition, EndMT contributes to the generation of cancer associated fibroblasts that are known to influence the tumor-microenvironment favorable for the tumor cells. EndMT is a form of the more widely known and studied Epithelial-to-Mesenchymal Transition (EMT). Like EMT, EndMT can be induced by transforming growth factor (TGF)-β. Indeed many studies have pointed to the important role of TGF-β receptor/Smad signaling and downstream targets, such as Snail transcriptional repressor in EndMT. By selective targeting of TGF-β receptor signaling pathological EndMT may be inhibited for the therapeutic benefit of patients with cancer and fibrosis.
Topics: Animals; Biomarkers; Cell Differentiation; Cell Transdifferentiation; Endothelial Cells; Fibrosis; Humans; Mesoderm; Neoplasms; Signal Transduction; Transforming Growth Factor beta
PubMed: 21866313
DOI: 10.1007/s00441-011-1222-6 -
Cell Adhesion & Migration 2011Cell migration is critical for proper development of the embryo and is also used by many cell types to perform their physiological function. For instance, cell migration... (Review)
Review
Cell migration is critical for proper development of the embryo and is also used by many cell types to perform their physiological function. For instance, cell migration is essential for immune cells to monitor the body and for epithelial cells to heal a wound whereas, in cancer cells, acquisition of migratory capabilities is a critical step towards malignancy. Migratory cells are often categorized into two groups: mesenchymal cells, produced by an epithelium-to-mesenchyme transition, that undergo solitary migration and epithelial-like cells which migrate collectively. However, on some occasions, mesenchymal cells may travel in large, dense groups and exhibit key features of collectively migrating cells such as coordination and cooperation. Here, using data published on Neural Crest cells, a highly invasive mesenchymal cell population that extensively migrate throughout the embryo, we explore the idea that other mesenchymal cells, including cancer cells, might be able to undergo collective cell migration under certain conditions and discuss how they could do so.
Topics: Animals; Cell Adhesion; Cell Movement; Embryonic Development; Mesoderm; Nervous System; Neural Crest
PubMed: 22274714
DOI: 10.4161/cam.5.6.18623 -
PloS One 2019Primed nephron progenitor cells (NPCs) appear in metanephric mesenchyme by E11.5 and differentiate in response to the inductive WNT9b signal from the ureteric bud....
Primed nephron progenitor cells (NPCs) appear in metanephric mesenchyme by E11.5 and differentiate in response to the inductive WNT9b signal from the ureteric bud. However, the NPC WNT-receptor complex is unknown. We obtained M15 cells from E10.5 mesonephric mesenchyme and systematically analyzed components required for canonical WNT9b-responsiveness. When M15 cells were transfected with a β-catenin luciferase reporter plasmid, exposure to recombinant WNT9b resulted in minimal luciferase activity. We then analyzed mRNA-expression of WNT-pathway components and identified Fzd1-6 and Lrp6 transcripts but not Rspo1. When M15 cells were treated with recombinant RSPO1 the response to transfected WNT9b was augmented 4.8-fold. Co-transfection of M15 cells with Fzd5 (but no other Fzd family member) further increased the WNT9b signal to 16.8-fold and siRNA knockdown of Fzd5 reduced the signal by 52%. Knockdown of Lrp6 resulted in 60% WNT9b signal reduction. We confirmed Fzd5, Lrp6 and Rspo1 mRNA expression in CITED1(+) NPCs from E15.5 embryonic mouse kidney. Thus, while many WNT signaling-pathway components are present by E10.5, optimum responsiveness of E11.5 cap mesenchyme requires that NPCs acquire RSPO1, FZD5 and LRP6.
Topics: Animals; Cells, Cultured; Mesoderm; Mice; Nephrons; Signal Transduction; Stem Cells; Wnt Proteins; beta Catenin
PubMed: 30978219
DOI: 10.1371/journal.pone.0215139 -
Development (Cambridge, England) Jul 2012Development of the metanephric kidney in mammals requires complex reciprocal tissue interactions between the ureteric epithelium and the mesenchyme. It is believed that...
Development of the metanephric kidney in mammals requires complex reciprocal tissue interactions between the ureteric epithelium and the mesenchyme. It is believed that Gdnf, produced in the metanephric mesenchyme, activates Ret signaling in the Wolffian duct to initiate the formation of the metanephros. However, the molecular mechanism for induction of Gdnf in the metanephric mesenchyme is not completely defined. Previous studies demonstrated that during the early stages of kidney development, loss of Osr1, Eya1, Pax2 or Wt1 gene function in the metanephric mesenchyme compromises the formation of the kidney. Moreover, it has been shown that the Hox11-Eya1-Pax2 complex activates the expression of Six2 and Gdnf in the metanephric mesenchyme to drive nephrogenesis. Here, we demonstrate that the orphan nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII, also known as Nr2f2) is required for the specification of the metanephric mesenchyme. Deletion of COUP-TFII at E7.5 results in improper differentiation of the metanephric mesenchyme and absence of essential developmental regulators, such as Eya1, Six2, Pax2 and Gdnf. Importantly, we show that COUP-TFII directly regulates the expression of both Eya1 and Wt1 in the metanephric mesenchyme. Our findings reveal, for the first time, that COUP-TFII plays a central role in the specification of metanephric fate and in the maintenance of metanephric mesenchyme proliferation and survival by acting as a crucial regulator of Eya1 and Wt1 expression.
Topics: Animals; COUP Transcription Factor II; Cell Differentiation; Cell Survival; Embryonic Development; Female; Gene Deletion; Gene Expression Regulation, Developmental; Glial Cell Line-Derived Neurotrophic Factor; Homeodomain Proteins; Intracellular Signaling Peptides and Proteins; Kidney; Male; Mesenchymal Stem Cells; Mesoderm; Mice; Nuclear Proteins; Organogenesis; PAX2 Transcription Factor; Pregnancy; Protein Tyrosine Phosphatases; Transcription Factors
PubMed: 22669823
DOI: 10.1242/dev.076299 -
World Journal of Gastroenterology May 2007Recent advances in cell and molecular radiobiology clearly showed that tissue response to radiation injury cannot be restricted to a simple cell-killing process, but... (Review)
Review
Recent advances in cell and molecular radiobiology clearly showed that tissue response to radiation injury cannot be restricted to a simple cell-killing process, but depends upon continuous and integrated pathogenic processes, involving cell differentiation and crosstalk between the various cellular components of the tissue within the extracellular matrix. Thus, the prior concept of primary cell target in which a single-cell type (whatever it's epithelial or endothelial cells) dictates the whole tissue response to radiation injury has to be replaced by the occurrence of coordinated multicellular response that may either lead to tissue recovery or to sequel development. In this context, the present review will focus on the maintenance of the radiation-induced wound healing and fibrogenic signals triggered by and through the microenvironment toward the mesenchymal cell compartment, and will highlight how sequential and sustained modifications in cell phenotypes will in cascade modify cell-to-cell interactions and tissue composition.
Topics: Cell Communication; Cell Differentiation; Fibrosis; Humans; Intestines; Mesoderm; Radiation Injuries; Radiotherapy
PubMed: 17569135
DOI: 10.3748/wjg.v13.i19.2675 -
American Journal of Physiology. Lung... May 2019Transcription factor 21 (Tcf21) is a basic helix-loop-helix transcription factor required for mesenchymal development in several organs. Others have demonstrated that...
Transcription factor 21 (Tcf21) is a basic helix-loop-helix transcription factor required for mesenchymal development in several organs. Others have demonstrated that Tcf21 is expressed in embryonic lung mesenchyme and that loss of Tcf21 results in a pulmonary hypoplasia phenotype. Although recent single-cell transcriptome analysis has described multiple mesenchymal cell types in the lung, few have characterized the Tcf21 expressing population. To explore the Tcf21 mesenchymal lineage, we traced Tcf21-expressing cells during embryogenesis and in the adult. Our results showed that Tcf21 progenitor cells at embryonic day (E)11.5 generated a subpopulation of fibroblasts and lipofibroblasts and a limited number of smooth muscle cells. After E15.5, Tcf21 progenitor cells exclusively become lipofibroblasts and interstitial fibroblasts. Lipid metabolism genes were highly expressed in perinatal and adult Tcf21 lineage cells. Overexpression of Tcf21 in primary neonatal lung fibroblasts led to increases in intracellular neutral lipids, suggesting a regulatory role for Tcf21 in lipofibroblast function. Collectively, our results reveal that Tcf21 expression after E15.5 delineates the lipofibroblast and a population of interstitial fibroblasts. The inducible Cre mouse line provides a novel method for identifying and manipulating the lipofibroblast.
Topics: Adipocytes; Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Cell Lineage; Cells, Cultured; Female; Fibroblasts; Gene Expression Regulation, Developmental; Gestational Age; Lipid Metabolism; Lung; Male; Mesoderm; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pregnancy
PubMed: 30675802
DOI: 10.1152/ajplung.00254.2018 -
Journal of Visualized Experiments : JoVE Apr 2013Orofacial clefts are the most frequent craniofacial defects, which affect 1.5 in 1,000 newborns worldwide. Orofacial clefting is caused by abnormal facial development....
Orofacial clefts are the most frequent craniofacial defects, which affect 1.5 in 1,000 newborns worldwide. Orofacial clefting is caused by abnormal facial development. In human and mouse, initial growth and patterning of the face relies on several small buds of tissue, the facial prominences. The face is derived from six main prominences: paired frontal nasal processes (FNP), maxillary prominences (MxP) and mandibular prominences (MdP). These prominences consist of swellings of mesenchyme that are encased in an overlying epithelium. Studies in multiple species have shown that signaling crosstalk between facial ectoderm and mesenchyme is critical for shaping the face. Yet, mechanistic details concerning the genes involved in these signaling relays are lacking. One way to gain a comprehensive understanding of gene expression, transcription factor binding, and chromatin marks associated with the developing facial ectoderm and mesenchyme is to isolate and characterize the separated tissue compartments. Here we present a method for separating facial ectoderm and mesenchyme at embryonic day (E) 10.5, a critical developmental stage in mouse facial formation that precedes fusion of the prominences. Our method is adapted from the approach we have previously used for dissecting facial prominences. In this earlier study we had employed inbred C57BL/6 mice as this strain has become a standard for genetics, genomics and facial morphology. Here, though, due to the more limited quantities of tissue available, we have utilized the outbred CD-1 strain that is cheaper to purchase, more robust for husbandry, and tending to produce more embryos (12-18) per litter than any inbred mouse strain. Following embryo isolation, neutral protease Dispase II was used to treat the whole embryo. Then, the facial prominences were dissected out, and the facial ectoderm was separated from the mesenchyme. This method keeps both the facial ectoderm and mesenchyme intact. The samples obtained using this methodology can be used for techniques including protein detection, chromatin immunoprecipitation (ChIP) assay, microarray studies, and RNA-seq.
Topics: Animals; Dissection; Ectoderm; Embryo, Mammalian; Face; Female; Mesoderm; Mice; Mice, Inbred C57BL; Pregnancy
PubMed: 23603693
DOI: 10.3791/50248 -
Developmental Dynamics : An Official... May 2011Msx1 and Msx2 encode homeodomain transcription factors that play a crucial role in limb development. However, the limb phenotype of the double Msx1(null/null)...
Msx1 and Msx2 encode homeodomain transcription factors that play a crucial role in limb development. However, the limb phenotype of the double Msx1(null/null) Msx2(null/null) mutant is difficult to analyze, particularly along the anteroposterior axis, because of the complex effects of the double mutation on both ectoderm- and mesoderm-derived structures. Namely, in the mutant, formation of the apical ectodermal ridge (AER) is impaired anteriorly and, consequently, the subjacent mesenchyme does not form. Using the Cre/loxP system, we investigated the respective roles of Msx genes in ectoderm and mesoderm by generating conditional mutant embryos with no Msx activity solely in the mesoderm. In these mutants, the integrity of the ectoderm-derived AER was maintained, allowing formation of the anterior mesenchyme. With this strategy, we demonstrate that mesenchymal expression of Msx1 and Msx2 is required for proper Shh and Bmp4 signaling to specify digit number and identity.
Topics: Animals; Cell Death; Cell Proliferation; Extremities; Homeodomain Proteins; In Situ Hybridization; Limb Buds; MSX1 Transcription Factor; Mesoderm; Mice; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 21465616
DOI: 10.1002/dvdy.22619 -
Nature Communications Nov 2019The extent of neocortical gyrification is an important determinant of a species' cognitive abilities, yet the mechanisms regulating cortical gyrification are poorly...
The extent of neocortical gyrification is an important determinant of a species' cognitive abilities, yet the mechanisms regulating cortical gyrification are poorly understood. We uncover long-range regulation of this process originating at the telencephalic dorsal midline, where levels of secreted Bmps are maintained by factors in both the neuroepithelium and the overlying mesenchyme. In the mouse, the combined loss of transcription factors Lmx1a and Lmx1b, selectively expressed in the midline neuroepithelium and the mesenchyme respectively, causes dorsal midline Bmp signaling to drop at early neural tube stages. This alters the spatial and temporal Wnt signaling profile of the dorsal midline cortical hem, which in turn causes gyrification of the distal neocortex. Our study uncovers early mesenchymal-neuroepithelial interactions that have long-range effects on neocortical gyrification and shows that lissencephaly in mice is actively maintained via redundant genetic regulation of dorsal midline development and signaling.
Topics: Animals; Female; Gene Expression Regulation, Developmental; LIM-Homeodomain Proteins; Male; Mesoderm; Mice; Mice, Inbred C57BL; Mice, Knockout; Neocortex; Neuroepithelial Cells; Signal Transduction; Transcription Factors; Wnt Proteins
PubMed: 31729356
DOI: 10.1038/s41467-019-12913-z