The Experts below are selected from a list of 20661 Experts worldwide ranked by ideXlab platform
Vladimir Toder - One of the best experts on this subject based on the ideXlab platform.
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teratogen induced apoptotic cell death does the apoptotic machinery act as a protector of embryos exposed to teratogens
Birth Defects Research Part C-embryo Today-reviews, 2005Co-Authors: Arkady Torchinsky, Amos Fein, Vladimir ToderAbstract:Considerable evidence has been collected demonstrating that many teratogens induce apoptotic cell death in Embryonic Structures that turn out to be malformed in fetuses and newborns. Apoptosis is a genetically regulated process that is realized by the activation of death and prosurvival signaling cascades, and the interplay between these cascades determines whether the cell exposed to apoptotic stimuli dies or survives. Therefore, there is intense interest in understanding how the apoptotic machinery functions in embryos exposed to teratogens. However, the interpretation of the results obtained remains problematic. The main problem is that excessive Embryonic cell death, regardless of its nature, if uncompensated for, ultimately leads to maldevelopment or Embryonic death. Therefore, we can easily interpret results when the intensity of teratogen-induced cell death and the severity or incidence of teratogeninduced anomalies directly correlate with each other. However, when teratogen-induced cell death is not followed by the formation of anomalies, a usual explanation is that teratogen-induced apoptotic cell death contributes to the renewal of teratogen-targeted cell populations by promoting the removal of injured cells. It is clear that such an explanation leaves vague the role of the antiapoptotic signaling mechanism (and, hence, the apoptotic machinery as a whole) with respect to protecting the embryo against teratogenic stress. In this review, we summarize the data from studies addressing the function of the apoptotic machinery in embryos exposed to teratogens, and then we discuss approaches to interpreting the results of these studies. We hypothesize that activation of a proapoptotic signaling in teratogen-targeted cell populations is a necessary condition for an antiapoptotic signaling that counteracts the process of maldevelopment to be activated. If such a scenario is true, we need to modify our approaches to choosing molecular targets for studies addressing this topic. Birth Defects Research (Part C) 75: 353–361, 2005. © 2006 Wiley-Liss, Inc.
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teratogen induced apoptotic cell death does the apoptotic machinery act as a protector of embryos exposed to teratogens
Birth Defects Research Part C-embryo Today-reviews, 2005Co-Authors: Arkady Torchinsky, Amos Fein, Vladimir ToderAbstract:Considerable evidence has been collected demonstrating that many teratogens induce apoptotic cell death in Embryonic Structures that turn out to be malformed in fetuses and newborns. Apoptosis is a genetically regulated process that is realized by the activation of death and pro-survival signaling cascades, and the interplay between these cascades determines whether the cell exposed to apoptotic stimuli dies or survives. Therefore, there is intense interest in understanding how the apoptotic machinery functions in embryos exposed to teratogens. However, the interpretation of the results obtained remains problematic. The main problem is that excessive Embryonic cell death, regardless of its nature, if uncompensated for, ultimately leads to maldevelopment or Embryonic death. Therefore, we can easily interpret results when the intensity of teratogen-induced cell death and the severity or incidence of teratogen-induced anomalies directly correlate with each other. However, when teratogen-induced cell death is not followed by the formation of anomalies, a usual explanation is that teratogen-induced apoptotic cell death contributes to the renewal of teratogen-targeted cell populations by promoting the removal of injured cells. It is clear that such an explanation leaves vague the role of the anti-apoptotic signaling mechanism (and, hence, the apoptotic machinery as a whole) with respect to protecting the embryo against teratogenic stress. In this review, we summarize the data from studies addressing the function of the apoptotic machinery in embryos exposed to teratogens, and then we discuss approaches to interpreting the results of these studies. We hypothesize that activation of a proapoptotic signaling in teratogen-targeted cell populations is a necessary condition for an anti-apoptotic signaling that counteracts the process of maldevelopment to be activated. If such a scenario is true, we need to modify our approaches to choosing molecular targets for studies addressing this topic.
Arkady Torchinsky - One of the best experts on this subject based on the ideXlab platform.
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microrna 34a is dispensable for p53 function as teratogenesis inducer
Archives of Toxicology, 2014Co-Authors: Lin He, Arkady Torchinsky, Noam ShomronAbstract:The tumor suppressor protein p53 is a powerful regulator of the embryo’s susceptibility to diverse teratogenic stimuli, functioning both as a teratogenesis inducer and suppressor. However, the targets that p53 engages to fulfill its functions remain largely undefined. We asked whether the microRNA (miRNA) miR-34 family, identified as one of the main targets of p53, mediates its function as a teratogenesis inducer. For this, pregnant ICR-, p53- and miR-34a-deficient mice, as well as rats, were exposed to 5-aza-2′-deoxycytidine (5-aza), a teratogen inducing limb reduction anomalies (LRA) of the hindlimbs in mice and either the hindlimbs or forelimbs in rats. Using hind- and forelimb buds of 5-aza-exposed embryos, we identified that the miR-34 family members are the most upregulated miRNAs in mouse and rat limb buds, with their increase level being significantly higher in limb buds destined for LRA. We showed that p53 mediates the 5-aza-induced miR-34 transcription followed by met proto-oncogene and growth-arrest-specific 1 target suppression in Embryonic limb buds. We demonstrated that p53 regulates the teratogenic response to 5-aza acting as a teratogenesis inducer albeit miR-34a deletion does not affect the susceptibility of mice to 5-aza. Overall, our study thoroughly characterizes the expression and regulation of miR-34 family in teratogen-resistant and teratogen-sensitive Embryonic Structures and discusses the involvement of epigenetic miRNA-mediated pathway(s) in induced teratogenesis.
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teratogen induced apoptotic cell death does the apoptotic machinery act as a protector of embryos exposed to teratogens
Birth Defects Research Part C-embryo Today-reviews, 2005Co-Authors: Arkady Torchinsky, Amos Fein, Vladimir ToderAbstract:Considerable evidence has been collected demonstrating that many teratogens induce apoptotic cell death in Embryonic Structures that turn out to be malformed in fetuses and newborns. Apoptosis is a genetically regulated process that is realized by the activation of death and prosurvival signaling cascades, and the interplay between these cascades determines whether the cell exposed to apoptotic stimuli dies or survives. Therefore, there is intense interest in understanding how the apoptotic machinery functions in embryos exposed to teratogens. However, the interpretation of the results obtained remains problematic. The main problem is that excessive Embryonic cell death, regardless of its nature, if uncompensated for, ultimately leads to maldevelopment or Embryonic death. Therefore, we can easily interpret results when the intensity of teratogen-induced cell death and the severity or incidence of teratogeninduced anomalies directly correlate with each other. However, when teratogen-induced cell death is not followed by the formation of anomalies, a usual explanation is that teratogen-induced apoptotic cell death contributes to the renewal of teratogen-targeted cell populations by promoting the removal of injured cells. It is clear that such an explanation leaves vague the role of the antiapoptotic signaling mechanism (and, hence, the apoptotic machinery as a whole) with respect to protecting the embryo against teratogenic stress. In this review, we summarize the data from studies addressing the function of the apoptotic machinery in embryos exposed to teratogens, and then we discuss approaches to interpreting the results of these studies. We hypothesize that activation of a proapoptotic signaling in teratogen-targeted cell populations is a necessary condition for an antiapoptotic signaling that counteracts the process of maldevelopment to be activated. If such a scenario is true, we need to modify our approaches to choosing molecular targets for studies addressing this topic. Birth Defects Research (Part C) 75: 353–361, 2005. © 2006 Wiley-Liss, Inc.
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teratogen induced apoptotic cell death does the apoptotic machinery act as a protector of embryos exposed to teratogens
Birth Defects Research Part C-embryo Today-reviews, 2005Co-Authors: Arkady Torchinsky, Amos Fein, Vladimir ToderAbstract:Considerable evidence has been collected demonstrating that many teratogens induce apoptotic cell death in Embryonic Structures that turn out to be malformed in fetuses and newborns. Apoptosis is a genetically regulated process that is realized by the activation of death and pro-survival signaling cascades, and the interplay between these cascades determines whether the cell exposed to apoptotic stimuli dies or survives. Therefore, there is intense interest in understanding how the apoptotic machinery functions in embryos exposed to teratogens. However, the interpretation of the results obtained remains problematic. The main problem is that excessive Embryonic cell death, regardless of its nature, if uncompensated for, ultimately leads to maldevelopment or Embryonic death. Therefore, we can easily interpret results when the intensity of teratogen-induced cell death and the severity or incidence of teratogen-induced anomalies directly correlate with each other. However, when teratogen-induced cell death is not followed by the formation of anomalies, a usual explanation is that teratogen-induced apoptotic cell death contributes to the renewal of teratogen-targeted cell populations by promoting the removal of injured cells. It is clear that such an explanation leaves vague the role of the anti-apoptotic signaling mechanism (and, hence, the apoptotic machinery as a whole) with respect to protecting the embryo against teratogenic stress. In this review, we summarize the data from studies addressing the function of the apoptotic machinery in embryos exposed to teratogens, and then we discuss approaches to interpreting the results of these studies. We hypothesize that activation of a proapoptotic signaling in teratogen-targeted cell populations is a necessary condition for an anti-apoptotic signaling that counteracts the process of maldevelopment to be activated. If such a scenario is true, we need to modify our approaches to choosing molecular targets for studies addressing this topic.
Megan Valencia - One of the best experts on this subject based on the ideXlab platform.
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oscillatory cortical forces promote three dimensional cell intercalations that shape the murine mandibular arch
Nature Communications, 2019Co-Authors: Hirotaka Tao, Min Zhu, Kimberly Lau, Owen Whitley, Mohammad Samani, Xiao Xiao, Xiao Xiao Chen, Noah A Hahn, Weifan Liu, Megan ValenciaAbstract:Multiple vertebrate Embryonic Structures such as organ primordia are composed of confluent cells. Although mechanisms that shape tissue sheets are increasingly understood, those which shape a volume of cells remain obscure. Here we show that 3D mesenchymal cell intercalations are essential to shape the mandibular arch of the mouse embryo. Using a genetically encoded vinculin tension sensor that we knock-in to the mouse genome, we show that cortical force oscillations promote these intercalations. Genetic loss- and gain-of-function approaches show that Wnt5a functions as a spatial cue to coordinate cell polarity and cytoskeletal oscillation. These processes diminish tissue rigidity and help cells to overcome the energy barrier to intercalation. YAP/TAZ and PIEZO1 serve as downstream effectors of Wnt5a-mediated actomyosin polarity and cytosolic calcium transients that orient and drive mesenchymal cell intercalations. These findings advance our understanding of how developmental pathways regulate biophysical properties and forces to shape a solid organ primordium. Morphogenesis of tissue sheets is well studied, but mechanisms that shape bulk tissues are unclear. Here, the authors show that mesenchymal cells intercalate in 3D to shape the mouse branchial arch, with cortical forces driving intercalations in a Wnt5a-, Yap/Taz- and Piezo1-dependent manner.
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oscillatory cortical forces promote three dimensional cell intercalations that shape the mandibular arch
bioRxiv, 2018Co-Authors: Hirotaka Tao, Min Zhu, Kimberly Lau, Owen Whitley, Mohammad Samani, Xiao Xiao, Xiao Xiao Chen, Noah A Hahn, Weifan Liu, Megan ValenciaAbstract:Multiple vertebrate Embryonic Structures such as organ primordia are composed of a volume of confluent cells. Although mechanisms that shape tissue sheets are increasingly understood, those which shape a volume of cells remain obscure. Here we show 3D mesenchymal cell intercalations, rather than cell divisions and biophysical tissue properties, are essential to shape the mandibular arch of the mouse embryo. Using a genetically encoded vinculin tension sensor, we show that cortical force oscillations promote these intercalations. Genetic loss and gain of function approaches show that Wnt5a functions as a spatial cue to coordinate cell polarity with cytoskeletal oscillation. YAP/TAZ and PIEZO1 serve as downstream effectors of Wnt5a-mediated actomyosin bias and cytosolic calcium transients, respectively, to ensure appropriate tissue form during growth. Our data support oriented 3D cell neighbour exchange as a conserved mechanism driving volumetric morphogenesis.
Amos Fein - One of the best experts on this subject based on the ideXlab platform.
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teratogen induced apoptotic cell death does the apoptotic machinery act as a protector of embryos exposed to teratogens
Birth Defects Research Part C-embryo Today-reviews, 2005Co-Authors: Arkady Torchinsky, Amos Fein, Vladimir ToderAbstract:Considerable evidence has been collected demonstrating that many teratogens induce apoptotic cell death in Embryonic Structures that turn out to be malformed in fetuses and newborns. Apoptosis is a genetically regulated process that is realized by the activation of death and prosurvival signaling cascades, and the interplay between these cascades determines whether the cell exposed to apoptotic stimuli dies or survives. Therefore, there is intense interest in understanding how the apoptotic machinery functions in embryos exposed to teratogens. However, the interpretation of the results obtained remains problematic. The main problem is that excessive Embryonic cell death, regardless of its nature, if uncompensated for, ultimately leads to maldevelopment or Embryonic death. Therefore, we can easily interpret results when the intensity of teratogen-induced cell death and the severity or incidence of teratogeninduced anomalies directly correlate with each other. However, when teratogen-induced cell death is not followed by the formation of anomalies, a usual explanation is that teratogen-induced apoptotic cell death contributes to the renewal of teratogen-targeted cell populations by promoting the removal of injured cells. It is clear that such an explanation leaves vague the role of the antiapoptotic signaling mechanism (and, hence, the apoptotic machinery as a whole) with respect to protecting the embryo against teratogenic stress. In this review, we summarize the data from studies addressing the function of the apoptotic machinery in embryos exposed to teratogens, and then we discuss approaches to interpreting the results of these studies. We hypothesize that activation of a proapoptotic signaling in teratogen-targeted cell populations is a necessary condition for an antiapoptotic signaling that counteracts the process of maldevelopment to be activated. If such a scenario is true, we need to modify our approaches to choosing molecular targets for studies addressing this topic. Birth Defects Research (Part C) 75: 353–361, 2005. © 2006 Wiley-Liss, Inc.
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teratogen induced apoptotic cell death does the apoptotic machinery act as a protector of embryos exposed to teratogens
Birth Defects Research Part C-embryo Today-reviews, 2005Co-Authors: Arkady Torchinsky, Amos Fein, Vladimir ToderAbstract:Considerable evidence has been collected demonstrating that many teratogens induce apoptotic cell death in Embryonic Structures that turn out to be malformed in fetuses and newborns. Apoptosis is a genetically regulated process that is realized by the activation of death and pro-survival signaling cascades, and the interplay between these cascades determines whether the cell exposed to apoptotic stimuli dies or survives. Therefore, there is intense interest in understanding how the apoptotic machinery functions in embryos exposed to teratogens. However, the interpretation of the results obtained remains problematic. The main problem is that excessive Embryonic cell death, regardless of its nature, if uncompensated for, ultimately leads to maldevelopment or Embryonic death. Therefore, we can easily interpret results when the intensity of teratogen-induced cell death and the severity or incidence of teratogen-induced anomalies directly correlate with each other. However, when teratogen-induced cell death is not followed by the formation of anomalies, a usual explanation is that teratogen-induced apoptotic cell death contributes to the renewal of teratogen-targeted cell populations by promoting the removal of injured cells. It is clear that such an explanation leaves vague the role of the anti-apoptotic signaling mechanism (and, hence, the apoptotic machinery as a whole) with respect to protecting the embryo against teratogenic stress. In this review, we summarize the data from studies addressing the function of the apoptotic machinery in embryos exposed to teratogens, and then we discuss approaches to interpreting the results of these studies. We hypothesize that activation of a proapoptotic signaling in teratogen-targeted cell populations is a necessary condition for an anti-apoptotic signaling that counteracts the process of maldevelopment to be activated. If such a scenario is true, we need to modify our approaches to choosing molecular targets for studies addressing this topic.
Berna Sozen - One of the best experts on this subject based on the ideXlab platform.
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self assembly of Embryonic and two extra Embryonic stem cell types into gastrulating embryo like Structures
Nature Cell Biology, 2018Co-Authors: Berna Sozen, Gianluca Amadei, Ran Wang, Ellen Na, Sylwia Czukiewska, Lia Chappell, Thierry Voet, Geert Michel, Naihe JingAbstract:Embryonic stem cells can be incorporated into the developing embryo and its germ line, but, when cultured alone, their ability to generate Embryonic Structures is restricted. They can interact with trophoblast stem cells to generate Structures that break symmetry and specify mesoderm, but their development is limited as the epithelial-mesenchymal transition of gastrulation cannot occur. Here, we describe a system that allows assembly of mouse Embryonic, trophoblast and extra-Embryonic endoderm stem cells into Structures that acquire the embryo's architecture with all distinct Embryonic and extra-Embryonic compartments. Strikingly, such embryo-like Structures develop to undertake the epithelial-mesenchymal transition, leading to mesoderm and then definitive endoderm specification. Spatial transcriptomic analyses demonstrate that these morphological transformations are underpinned by gene expression patterns characteristic of gastrulating embryos. This demonstrates the remarkable ability of three stem cell types to self-assemble in vitro into gastrulating embryo-like Structures undertaking spatio-temporal events of the gastrulating mammalian embryo.