The Experts below are selected from a list of 801 Experts worldwide ranked by ideXlab platform
Harukazu Nakamura - One of the best experts on this subject based on the ideXlab platform.
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Pea3 determines the isthmus region at the downstream of Fgf8-Ras-ERK signaling pathway.
Development growth & differentiation, 2015Co-Authors: Hidekiyo Harada, Tatsuya Sato, Minoru Omi, Harukazu NakamuraAbstract:It has been shown that strong Fgf8 signal activates Ras-ERK signaling pathway to determine Metencephalon, which consists of rhombomere 1 (r1), where the cerebellum differentiates, and isthmus (r0). The present study was undertaken to check if Ets type transcription factor Pea3 functions downstream of Ras-ERK signaling to determine Metencephalon. Pea3 misexpression resulted in repression of Otx2 expression in the mesencephalon, induction of Gbx2 and Fgf8 expression in the mesencephalon, and differentiation of the trochlear neurons in the posterior mesencephalon. Fate change of the tectum to the cerebellum did not occur. Repression of Pea3 function by misexpressing the chimeric molecule of Engrailed repressor domain EH1 and Pea3 (eh1-Pea3) resulted in induction of Otx2 expression in the Metencephalon, repression of Gbx2 and Fgf8 expression in the Metencephalon, and differentiation of the oculomotor neurons in the isthmus. It was concluded that Pea3 plays a pivotal role in determination of the isthmus (r0) property downstream of Fgf8-Ras-ERK signaling.
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Engrailed and tectum development.
Development growth & differentiation, 2015Co-Authors: Minoru Omi, Harukazu NakamuraAbstract:The optic tectum is a visual center of nonmammalian vertebrates derived from the mesencephalon. In this review, function of Engrailed (En) in tectum development is reviewed. En plays crucial roles at three steps of tectum development. First, Engrailed is expressed in the mesencephalon and the Metencephalon and essential for the regionalization of the mesencephalon. En is expressed in a gradient of caudal-to-rostral in the tectum primordial, and regulates the rostrocaudal polarity of the tectum. In the advanced stage of tectum development, En is expressed in a lamina-specific manner and it is suggested that En regulates cell migration in the tectal laminar formation.
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Activation of Ras-ERK pathway by Fgf8 and its downregulation by Sprouty2 for the isthmus organizing activity.
Developmental Biology, 2009Co-Authors: Asuka Suzuki-hirano, Hidekiyo Harada, Tatsuya Sato, Harukazu NakamuraAbstract:Abstract In the previous studies, we showed that strong Fgf8 signaling activates the Ras-ERK pathway to induce cerebellum. Here, we show importance of negative regulation following activation of this pathway for proper regionalization of mesencephalon and Metencephalon in chick embryos. ‘Prolonged’ activation of ERK by misexpression of Fgf8b and dominant-negative Sprouty2 (dnSprouty2) did not change the fate of the mesencephalic alar plate. Downregulation of ERK activity using an MEK inhibitor, U0126, or by tetracycline-dependent Tet-off system after co-expression of Fgf8b and dnSprouty2 forced the mesencephalic alar plate to differentiate into cerebellum. We then paid attention to Mkp3. After misexpression of dnMkp3 and Fgf8b, slight downregulation of ERK activity occurred, which may be due to Sprouty2, and the mesencephalon transformed to the isthmus-like structure. The results indicate that ERK must be once upregulated and then be downregulated for cerebellar differentiation and that differential ERK activity level established by negative regulators receiving Fgf8 signal may determine regional specificity of mesencephalon and Metencephalon.
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Activation of Ras-ERK pathway by Fgf8 and its downregulation by Sprouty2 for the isthmus organizing activity
Nature Precedings, 2008Co-Authors: Asuka Suzuki-hirano, Tatsuya Sato, Harukazu NakamuraAbstract:In the previous studies, we showed that strong Fgf8 signaling activates the Ras-ERK pathway to induce cerebellum. Here, we show importance of negative regulation of this pathway. 'Prolonged' activation of ERK by misexpression of Fgf8b and dominant-negative Sprouty2 ( dnSprouty2 ) did not change the fate of the mesencephalic alar plate. Downregulation of ERK activity using a MEK inhibitor, U0126, or by tetracycline dependent Tet-off system after co-expression of Fgf8b and dnSprouty2 , forced the mesencephalic alar plate to differentiate into cerebellum. We then paid attention to Mkp3. After misexpression of dnMkp3 and Fgf8b , slight downregulation of ERK activity occurred, which may be due to Sprouty2, and the mesencephalon transformed to the isthmus-like structure. The results indicate that ERK must be once upregulated and then be downregulated for cerebellar differentiation, and that differential ERK activity level established by negative regulators receiving Fgf8 signal may determine regional specificity of mesencephalon and Metencephalon.
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Isthmus organizer for mesencephalon and Metencephalon.
Development growth & differentiation, 2008Co-Authors: Harukazu Nakamura, Tatsuya Sato, Asuka Suzuki-hiranoAbstract:The vertebrate central nervous system is elaborated from a simple neural tube. Brain vesicles formation is the first sign of regionalization. Classical transplantation using quail and chick embryos revealed that the mesencephalon-Metencephalon boundary (isthmus) functions as an organizer of the mesencephalon and Metencephalon. Fgf8 is accepted as a main organizing molecule of the isthmus. Strong Fgf8 signal activates the Ras-ERK signaling pathway to differentiate the cerebellum. In this review, the historical background of the means of identifying the isthmus organizer and the molecular mechanisms of signal transduction for tectum and cerebellum differentiation is reviewed.
Tatsuya Sato - One of the best experts on this subject based on the ideXlab platform.
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Pea3 determines the isthmus region at the downstream of Fgf8-Ras-ERK signaling pathway.
Development growth & differentiation, 2015Co-Authors: Hidekiyo Harada, Tatsuya Sato, Minoru Omi, Harukazu NakamuraAbstract:It has been shown that strong Fgf8 signal activates Ras-ERK signaling pathway to determine Metencephalon, which consists of rhombomere 1 (r1), where the cerebellum differentiates, and isthmus (r0). The present study was undertaken to check if Ets type transcription factor Pea3 functions downstream of Ras-ERK signaling to determine Metencephalon. Pea3 misexpression resulted in repression of Otx2 expression in the mesencephalon, induction of Gbx2 and Fgf8 expression in the mesencephalon, and differentiation of the trochlear neurons in the posterior mesencephalon. Fate change of the tectum to the cerebellum did not occur. Repression of Pea3 function by misexpressing the chimeric molecule of Engrailed repressor domain EH1 and Pea3 (eh1-Pea3) resulted in induction of Otx2 expression in the Metencephalon, repression of Gbx2 and Fgf8 expression in the Metencephalon, and differentiation of the oculomotor neurons in the isthmus. It was concluded that Pea3 plays a pivotal role in determination of the isthmus (r0) property downstream of Fgf8-Ras-ERK signaling.
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Activation of Ras-ERK pathway by Fgf8 and its downregulation by Sprouty2 for the isthmus organizing activity.
Developmental Biology, 2009Co-Authors: Asuka Suzuki-hirano, Hidekiyo Harada, Tatsuya Sato, Harukazu NakamuraAbstract:Abstract In the previous studies, we showed that strong Fgf8 signaling activates the Ras-ERK pathway to induce cerebellum. Here, we show importance of negative regulation following activation of this pathway for proper regionalization of mesencephalon and Metencephalon in chick embryos. ‘Prolonged’ activation of ERK by misexpression of Fgf8b and dominant-negative Sprouty2 (dnSprouty2) did not change the fate of the mesencephalic alar plate. Downregulation of ERK activity using an MEK inhibitor, U0126, or by tetracycline-dependent Tet-off system after co-expression of Fgf8b and dnSprouty2 forced the mesencephalic alar plate to differentiate into cerebellum. We then paid attention to Mkp3. After misexpression of dnMkp3 and Fgf8b, slight downregulation of ERK activity occurred, which may be due to Sprouty2, and the mesencephalon transformed to the isthmus-like structure. The results indicate that ERK must be once upregulated and then be downregulated for cerebellar differentiation and that differential ERK activity level established by negative regulators receiving Fgf8 signal may determine regional specificity of mesencephalon and Metencephalon.
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Activation of Ras-ERK pathway by Fgf8 and its downregulation by Sprouty2 for the isthmus organizing activity
Nature Precedings, 2008Co-Authors: Asuka Suzuki-hirano, Tatsuya Sato, Harukazu NakamuraAbstract:In the previous studies, we showed that strong Fgf8 signaling activates the Ras-ERK pathway to induce cerebellum. Here, we show importance of negative regulation of this pathway. 'Prolonged' activation of ERK by misexpression of Fgf8b and dominant-negative Sprouty2 ( dnSprouty2 ) did not change the fate of the mesencephalic alar plate. Downregulation of ERK activity using a MEK inhibitor, U0126, or by tetracycline dependent Tet-off system after co-expression of Fgf8b and dnSprouty2 , forced the mesencephalic alar plate to differentiate into cerebellum. We then paid attention to Mkp3. After misexpression of dnMkp3 and Fgf8b , slight downregulation of ERK activity occurred, which may be due to Sprouty2, and the mesencephalon transformed to the isthmus-like structure. The results indicate that ERK must be once upregulated and then be downregulated for cerebellar differentiation, and that differential ERK activity level established by negative regulators receiving Fgf8 signal may determine regional specificity of mesencephalon and Metencephalon.
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Isthmus organizer for mesencephalon and Metencephalon.
Development growth & differentiation, 2008Co-Authors: Harukazu Nakamura, Tatsuya Sato, Asuka Suzuki-hiranoAbstract:The vertebrate central nervous system is elaborated from a simple neural tube. Brain vesicles formation is the first sign of regionalization. Classical transplantation using quail and chick embryos revealed that the mesencephalon-Metencephalon boundary (isthmus) functions as an organizer of the mesencephalon and Metencephalon. Fgf8 is accepted as a main organizing molecule of the isthmus. Strong Fgf8 signal activates the Ras-ERK signaling pathway to differentiate the cerebellum. In this review, the historical background of the means of identifying the isthmus organizer and the molecular mechanisms of signal transduction for tectum and cerebellum differentiation is reviewed.
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Regulation of isthmic Fgf8 signal by sprouty2.
Development (Cambridge England), 2004Co-Authors: Asuka Suzuki-hirano, Tatsuya Sato, Harukazu NakamuraAbstract:Fgf8 functions as an organizer at the mes/metencephalic boundary (isthmus). We showed that a strong Fgf8 signal activates the Ras-ERK signaling pathway to organize cerebellar differentiation. Sprouty2 is expressed in an overlapping manner to Fgf8, and is induced by Fgf8. Its function, however, is indicated to antagonize Ras-ERK signaling. Here, we show the regulation of Fgf8 signaling in relation to Sprouty2. sprouty2 expression was induced very rapidly by Fgf8b, but interfered with ERK activation. sprouty2 misexpression resulted in a fate change of the presumptive Metencephalon to the mesencephalon. Misexpression of a dominant negative form of Sprouty2 augmented ERK activation, and resulted in anterior shift of the posterior border of the tectum. The results indicate that Fgf8 activates the Ras-ERK signaling pathway to differentiate the cerebellum, and that the hyper- or hypo-signaling of this pathway affects the fate of the brain vesicles. Sprouty2 may regulate the Fgf8-Ras-ERK signaling pathway for the proper regionalization of the Metencephalon and mesencephalon.
Asuka Suzuki-hirano - One of the best experts on this subject based on the ideXlab platform.
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Activation of Ras-ERK pathway by Fgf8 and its downregulation by Sprouty2 for the isthmus organizing activity.
Developmental Biology, 2009Co-Authors: Asuka Suzuki-hirano, Hidekiyo Harada, Tatsuya Sato, Harukazu NakamuraAbstract:Abstract In the previous studies, we showed that strong Fgf8 signaling activates the Ras-ERK pathway to induce cerebellum. Here, we show importance of negative regulation following activation of this pathway for proper regionalization of mesencephalon and Metencephalon in chick embryos. ‘Prolonged’ activation of ERK by misexpression of Fgf8b and dominant-negative Sprouty2 (dnSprouty2) did not change the fate of the mesencephalic alar plate. Downregulation of ERK activity using an MEK inhibitor, U0126, or by tetracycline-dependent Tet-off system after co-expression of Fgf8b and dnSprouty2 forced the mesencephalic alar plate to differentiate into cerebellum. We then paid attention to Mkp3. After misexpression of dnMkp3 and Fgf8b, slight downregulation of ERK activity occurred, which may be due to Sprouty2, and the mesencephalon transformed to the isthmus-like structure. The results indicate that ERK must be once upregulated and then be downregulated for cerebellar differentiation and that differential ERK activity level established by negative regulators receiving Fgf8 signal may determine regional specificity of mesencephalon and Metencephalon.
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Activation of Ras-ERK pathway by Fgf8 and its downregulation by Sprouty2 for the isthmus organizing activity
Nature Precedings, 2008Co-Authors: Asuka Suzuki-hirano, Tatsuya Sato, Harukazu NakamuraAbstract:In the previous studies, we showed that strong Fgf8 signaling activates the Ras-ERK pathway to induce cerebellum. Here, we show importance of negative regulation of this pathway. 'Prolonged' activation of ERK by misexpression of Fgf8b and dominant-negative Sprouty2 ( dnSprouty2 ) did not change the fate of the mesencephalic alar plate. Downregulation of ERK activity using a MEK inhibitor, U0126, or by tetracycline dependent Tet-off system after co-expression of Fgf8b and dnSprouty2 , forced the mesencephalic alar plate to differentiate into cerebellum. We then paid attention to Mkp3. After misexpression of dnMkp3 and Fgf8b , slight downregulation of ERK activity occurred, which may be due to Sprouty2, and the mesencephalon transformed to the isthmus-like structure. The results indicate that ERK must be once upregulated and then be downregulated for cerebellar differentiation, and that differential ERK activity level established by negative regulators receiving Fgf8 signal may determine regional specificity of mesencephalon and Metencephalon.
-
Isthmus organizer for mesencephalon and Metencephalon.
Development growth & differentiation, 2008Co-Authors: Harukazu Nakamura, Tatsuya Sato, Asuka Suzuki-hiranoAbstract:The vertebrate central nervous system is elaborated from a simple neural tube. Brain vesicles formation is the first sign of regionalization. Classical transplantation using quail and chick embryos revealed that the mesencephalon-Metencephalon boundary (isthmus) functions as an organizer of the mesencephalon and Metencephalon. Fgf8 is accepted as a main organizing molecule of the isthmus. Strong Fgf8 signal activates the Ras-ERK signaling pathway to differentiate the cerebellum. In this review, the historical background of the means of identifying the isthmus organizer and the molecular mechanisms of signal transduction for tectum and cerebellum differentiation is reviewed.
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Regulation of isthmic Fgf8 signal by sprouty2.
Development (Cambridge England), 2004Co-Authors: Asuka Suzuki-hirano, Tatsuya Sato, Harukazu NakamuraAbstract:Fgf8 functions as an organizer at the mes/metencephalic boundary (isthmus). We showed that a strong Fgf8 signal activates the Ras-ERK signaling pathway to organize cerebellar differentiation. Sprouty2 is expressed in an overlapping manner to Fgf8, and is induced by Fgf8. Its function, however, is indicated to antagonize Ras-ERK signaling. Here, we show the regulation of Fgf8 signaling in relation to Sprouty2. sprouty2 expression was induced very rapidly by Fgf8b, but interfered with ERK activation. sprouty2 misexpression resulted in a fate change of the presumptive Metencephalon to the mesencephalon. Misexpression of a dominant negative form of Sprouty2 augmented ERK activation, and resulted in anterior shift of the posterior border of the tectum. The results indicate that Fgf8 activates the Ras-ERK signaling pathway to differentiate the cerebellum, and that the hyper- or hypo-signaling of this pathway affects the fate of the brain vesicles. Sprouty2 may regulate the Fgf8-Ras-ERK signaling pathway for the proper regionalization of the Metencephalon and mesencephalon.
Hidekiyo Harada - One of the best experts on this subject based on the ideXlab platform.
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Pea3 determines the isthmus region at the downstream of Fgf8-Ras-ERK signaling pathway.
Development growth & differentiation, 2015Co-Authors: Hidekiyo Harada, Tatsuya Sato, Minoru Omi, Harukazu NakamuraAbstract:It has been shown that strong Fgf8 signal activates Ras-ERK signaling pathway to determine Metencephalon, which consists of rhombomere 1 (r1), where the cerebellum differentiates, and isthmus (r0). The present study was undertaken to check if Ets type transcription factor Pea3 functions downstream of Ras-ERK signaling to determine Metencephalon. Pea3 misexpression resulted in repression of Otx2 expression in the mesencephalon, induction of Gbx2 and Fgf8 expression in the mesencephalon, and differentiation of the trochlear neurons in the posterior mesencephalon. Fate change of the tectum to the cerebellum did not occur. Repression of Pea3 function by misexpressing the chimeric molecule of Engrailed repressor domain EH1 and Pea3 (eh1-Pea3) resulted in induction of Otx2 expression in the Metencephalon, repression of Gbx2 and Fgf8 expression in the Metencephalon, and differentiation of the oculomotor neurons in the isthmus. It was concluded that Pea3 plays a pivotal role in determination of the isthmus (r0) property downstream of Fgf8-Ras-ERK signaling.
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Activation of Ras-ERK pathway by Fgf8 and its downregulation by Sprouty2 for the isthmus organizing activity.
Developmental Biology, 2009Co-Authors: Asuka Suzuki-hirano, Hidekiyo Harada, Tatsuya Sato, Harukazu NakamuraAbstract:Abstract In the previous studies, we showed that strong Fgf8 signaling activates the Ras-ERK pathway to induce cerebellum. Here, we show importance of negative regulation following activation of this pathway for proper regionalization of mesencephalon and Metencephalon in chick embryos. ‘Prolonged’ activation of ERK by misexpression of Fgf8b and dominant-negative Sprouty2 (dnSprouty2) did not change the fate of the mesencephalic alar plate. Downregulation of ERK activity using an MEK inhibitor, U0126, or by tetracycline-dependent Tet-off system after co-expression of Fgf8b and dnSprouty2 forced the mesencephalic alar plate to differentiate into cerebellum. We then paid attention to Mkp3. After misexpression of dnMkp3 and Fgf8b, slight downregulation of ERK activity occurred, which may be due to Sprouty2, and the mesencephalon transformed to the isthmus-like structure. The results indicate that ERK must be once upregulated and then be downregulated for cerebellar differentiation and that differential ERK activity level established by negative regulators receiving Fgf8 signal may determine regional specificity of mesencephalon and Metencephalon.
Minoru Omi - One of the best experts on this subject based on the ideXlab platform.
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Pea3 determines the isthmus region at the downstream of Fgf8-Ras-ERK signaling pathway.
Development growth & differentiation, 2015Co-Authors: Hidekiyo Harada, Tatsuya Sato, Minoru Omi, Harukazu NakamuraAbstract:It has been shown that strong Fgf8 signal activates Ras-ERK signaling pathway to determine Metencephalon, which consists of rhombomere 1 (r1), where the cerebellum differentiates, and isthmus (r0). The present study was undertaken to check if Ets type transcription factor Pea3 functions downstream of Ras-ERK signaling to determine Metencephalon. Pea3 misexpression resulted in repression of Otx2 expression in the mesencephalon, induction of Gbx2 and Fgf8 expression in the mesencephalon, and differentiation of the trochlear neurons in the posterior mesencephalon. Fate change of the tectum to the cerebellum did not occur. Repression of Pea3 function by misexpressing the chimeric molecule of Engrailed repressor domain EH1 and Pea3 (eh1-Pea3) resulted in induction of Otx2 expression in the Metencephalon, repression of Gbx2 and Fgf8 expression in the Metencephalon, and differentiation of the oculomotor neurons in the isthmus. It was concluded that Pea3 plays a pivotal role in determination of the isthmus (r0) property downstream of Fgf8-Ras-ERK signaling.
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Engrailed and tectum development.
Development growth & differentiation, 2015Co-Authors: Minoru Omi, Harukazu NakamuraAbstract:The optic tectum is a visual center of nonmammalian vertebrates derived from the mesencephalon. In this review, function of Engrailed (En) in tectum development is reviewed. En plays crucial roles at three steps of tectum development. First, Engrailed is expressed in the mesencephalon and the Metencephalon and essential for the regionalization of the mesencephalon. En is expressed in a gradient of caudal-to-rostral in the tectum primordial, and regulates the rostrocaudal polarity of the tectum. In the advanced stage of tectum development, En is expressed in a lamina-specific manner and it is suggested that En regulates cell migration in the tectal laminar formation.