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Linda Z Holland - One of the best experts on this subject based on the ideXlab platform.
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Retinoic acid and Wnt/β-catenin have complementary roles in anterior/posterior Patterning embryos of the basal chordate amphioxus
Developmental biology, 2009Co-Authors: Takayuki Onai, Michael Schubert, Nicholas D Holland, Hsiu-chin Lin, Demian Koop, Peter W. Osborne, Susana Álvarez, Rosana Alvarez, Linda Z HollandAbstract:Abstract A role for Wnt/β-catenin signaling in axial Patterning has been demonstrated in animals as basal as cnidarians, while roles in axial Patterning for retinoic acid (RA) probably evolved in the deuterostomes and may be chordate-specific. In vertebrates, these two pathways interact both directly and indirectly. To investigate the evolutionary origins of interactions between these two pathways, we manipulated Wnt/β-catenin and RA signaling in the basal chordate amphioxus during the gastrula stage, which is the RA-sensitive period for anterior/posterior (A/P) Patterning. The results show that Wnt/β-catenin and RA signaling have distinctly different roles in Patterning the A/P axis of the amphioxus gastrula. Wnt/β-catenin specifies the identity of the ends of the embryo (high Wnt = posterior; low Wnt = anterior) but not intervening positions. Thus, upregulation of Wnt/β-catenin signaling induces ectopic expression of posterior markers at the anterior tip of the embryo. In contrast, RA specifies position along the A/P axis, but not the identity of the ends of the embryo—increased RA signaling strongly affects the domains of Hox expression along the A/P axis but has little or no effect on the expression of either anterior or posterior markers. Although the two pathways may both influence such things as specification of neuronal identity, interactions between them in A/P Patterning appear to be minimal.
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a retinoic acid hox hierarchy controls both anterior posterior Patterning and neuronal specification in the developing central nervous system of the cephalochordate amphioxus
Developmental Biology, 2006Co-Authors: Michael Schubert, Nicholas D Holland, Vincent Laudet, Linda Z HollandAbstract:Retinoic acid (RA) mediates both anterior/posterior Patterning and neuronal specification in the vertebrate central nervous system (CNS). However, the molecular mechanisms downstream of RA are not well understood. To investigate these mechanisms, we used the invertebrate chordate amphioxus, in which the CNS, although containing only about 20,000 neurons in adults, like the vertebrate CNS, has a forebrain, midbrain, hindbrain, and spinal cord and is regionalized by RA-signaling. Here we show, first, that domains of genes with expression normally limited to diencephalon and midbrain are generally not affected by altered RA-signaling, second, that contrary to previous reports, not only Hox1, 3, and 4, but also Hox2 and Hox6 are collinearly expressed in the amphioxus CNS, and third, that collinear expression of all these Hox genes is controlled by RA-signaling. Finally, we show that Hox1 is involved in mediating both the role of RA-signaling in regionalization of the hindbrain and in specification of hindbrain motor neurons. Thus, morpholino knock-down of the single amphioxus Hox1 mimics the effects of treatments with an RA-antagonist. This analysis establishes RA-dependent regulation of collinear Hox expression as a feature common to the chordate CNS and indicates that the RA-Hox hierarchy functions both in proper anterior/posterior Patterning of the developing CNS and in specification of neuronal identity.
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A retinoic acid-Hox hierarchy controls both anterior/posterior Patterning and neuronal specification in the developing central nervous system of the cephalochordate amphioxus.
Developmental biology, 2006Co-Authors: Michael Schubert, Nicholas D Holland, Vincent Laudet, Linda Z HollandAbstract:Retinoic acid (RA) mediates both anterior/posterior Patterning and neuronal specification in the vertebrate central nervous system (CNS). However, the molecular mechanisms downstream of RA are not well understood. To investigate these mechanisms, we used the invertebrate chordate amphioxus, in which the CNS, although containing only about 20,000 neurons in adults, like the vertebrate CNS, has a forebrain, midbrain, hindbrain, and spinal cord and is regionalized by RA-signaling. Here we show, first, that domains of genes with expression normally limited to diencephalon and midbrain are generally not affected by altered RA-signaling, second, that contrary to previous reports, not only Hox1, 3, and 4, but also Hox2 and Hox6 are collinearly expressed in the amphioxus CNS, and third, that collinear expression of all these Hox genes is controlled by RA-signaling. Finally, we show that Hox1 is involved in mediating both the role of RA-signaling in regionalization of the hindbrain and in specification of hindbrain motor neurons. Thus, morpholino knock-down of the single amphioxus Hox1 mimics the effects of treatments with an RA-antagonist. This analysis establishes RA-dependent regulation of collinear Hox expression as a feature common to the chordate CNS and indicates that the RA-Hox hierarchy functions both in proper anterior/posterior Patterning of the developing CNS and in specification of neuronal identity.
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Heads or tails? Amphioxus and the evolution of Anterior-Posterior Patterning in deuterostomes.
Developmental biology, 2002Co-Authors: Linda Z HollandAbstract:In Xenopus, the canonical Wnt-signaling pathway acting through beta-catenin functions both in establishing the dorso-ventral axis and in Patterning the Anterior-Posterior axis. This pathway also acts in Patterning the animal-vegetal axis in sea urchins. However, because sea urchin development is typically indirect, and adult sea urchins have pentamerous symmetry and lack a longitudinal nerve cord, it has not been clear how the roles of the canonical Wnt-signaling pathway in axial Patterning in sea urchins and vertebrates are evolutionarily related. The developmental expression patterns of Notch, brachyury, caudal, and eight Wnt genes have now been determined for the invertebrate chordate Amphioxus, which, like sea urchins, has an early embryo that gastrulates by invagination, but like vertebrates, has a later embryo with a dorsal hollow nerve cord that elongates posteriorly from a tail bud. Comparisons of Amphioxus with other deuterostomes suggest that Patterning of the ancestral deuterostome embryo along its Anterior-Posterior axis during the late blastula and subsequent stages involved a posterior signaling center including Wnts, Notch, and transcription factors such as brachyury and caudal. In tunicate embryos, in which cell numbers are reduced and cell fates largely determined during cleavage stages, only vestiges of this signaling center are still apparent; these include localization of Wnt-5 mRNA to the posterior cytoplasm shortly after fertilization and localization of beta-catenin to vegetal nuclei during cleavage stages. Neither in tunicates nor in Amphioxus is there any evidence that the canonical Wnt-signaling pathway functions in establishment of the dorso-ventral axis. Thus, roles for Wnt-signaling in dorso-ventral Patterning of embryos may be a vertebrate innovation that arose in connection with the evolution of yolky eggs and gastrulation by extensive involution.
Tohru Ishitani - One of the best experts on this subject based on the ideXlab platform.
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Cell competition corrects noisy Wnt morphogen gradients to achieve robust Patterning in the zebrafish embryo
Nature Communications, 2019Co-Authors: Yuki Akieda, Shohei Ogamino, Hironobu Furuie, Shizuka Ishitani, Ryutaro Akiyoshi, Takamasa Masuda, Jumpei Nogami, Yasuyuki Ohkawa, Nobuyuki Shimizu, Tohru IshitaniAbstract:Gradients of morphogens such as Wnt provide instructive cues for cell identities during development. Here, the authors report that in the developing zebrafish embryo, cell competition and elimination of unfit cells are required for proper Wnt gradient formation.AbstractMorphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradients. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signalling gradient, which acts as a morphogen to establish embryonic Anterior-Posterior Patterning, identify that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin gradient formation and consequent Anterior-Posterior Patterning. Because this gradient controls Patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.
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Cell competition corrects noisy Wnt morphogen gradients to achieve robust Patterning in the zebrafish embryo
Nature communications, 2019Co-Authors: Yuki Akieda, Shohei Ogamino, Hironobu Furuie, Shizuka Ishitani, Ryutaro Akiyoshi, Takamasa Masuda, Jumpei Nogami, Yasuyuki Ohkawa, Nobuyuki Shimizu, Tohru IshitaniAbstract:Morphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradients. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signalling gradient, which acts as a morphogen to establish embryonic Anterior-Posterior Patterning, identify that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin gradient formation and consequent Anterior-Posterior Patterning. Because this gradient controls Patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.
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Cell competition corrects noisy Wnt morphogen gradients to achieve robust Patterning
2018Co-Authors: Yuki Akieda, Shohei Ogamino, Hironobu Furuie, Shizuka Ishitani, Ryutaro Akiyoshi, Takamasa Masuda, Jumpei Nogami, Yasuyuki Ohkawa, Nobuyuki Shimizu, Tohru IshitaniAbstract:Morphogen signaling forms an activity gradient and instructs cell identities in a signaling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signaling and consequent noisy morphogen gradient. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signaling-gradient, which acts as a morphogen to establish embryonic Anterior-Posterior Patterning, revealed that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the Wnt/β-catenin-gradient. Communication between the unfit and neighboring fit cells via cadherin proteins stimulates the apoptosis of the unfit cells by activating Smad signaling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin-gradient formation and consequent Anterior-Posterior Patterning. Because this gradient controls Patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.
Carlos F Ibanez - One of the best experts on this subject based on the ideXlab platform.
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growth differentiation factor 11 signals through the transforming growth factor β receptor alk5 to regionalize the anterior posterior axis
EMBO Reports, 2006Co-Authors: Olov Andersson, Eva Reissmann, Carlos F IbanezAbstract:Growth differentiation factor 11 (GDF11) contributes to regionalize the mouse embryo along its anterior–posterior axis by regulating the expression of Hox genes. The identity of the receptors that mediate GDF11 signalling during embryogenesis remains unclear. Here, we show that GDF11 can interact with type I receptors ALK4, ALK5 and ALK7, but predominantly uses ALK4 and ALK5 to activate a Smad3-dependent reporter gene. Alk5 mutant embryos showed malformations in anterior–posterior Patterning, including the lack of expression of the posterior determinant Hoxc10, that resemble defects found in Gdf11-null mutants. A heterozygous mutation in Alk5, but not in Alk4 or Alk7, potentiated Gdf11−/−-like phenotypes in vertebral, kidney and palate development in an Acvr2b−/− background, indicating a genetic interaction between the two receptor genes. Thus, the transforming growth factor-β (TGF-β) receptor ALK5, which until now has only been associated with the biological functions of TGF-β1 to TGF-β3 proteins, mediates GDF11 signalling during embryogenesis.
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Growth differentiation factor 11 signals through the transforming growth factor‐β receptor ALK5 to regionalize the anterior–posterior axis
EMBO Reports, 2006Co-Authors: Olov Andersson, Eva Reissmann, Carlos F IbanezAbstract:Growth differentiation factor 11 (GDF11) contributes to regionalize the mouse embryo along its anterior–posterior axis by regulating the expression of Hox genes. The identity of the receptors that mediate GDF11 signalling during embryogenesis remains unclear. Here, we show that GDF11 can interact with type I receptors ALK4, ALK5 and ALK7, but predominantly uses ALK4 and ALK5 to activate a Smad3-dependent reporter gene. Alk5 mutant embryos showed malformations in anterior–posterior Patterning, including the lack of expression of the posterior determinant Hoxc10, that resemble defects found in Gdf11-null mutants. A heterozygous mutation in Alk5, but not in Alk4 or Alk7, potentiated Gdf11−/−-like phenotypes in vertebral, kidney and palate development in an Acvr2b−/− background, indicating a genetic interaction between the two receptor genes. Thus, the transforming growth factor-β (TGF-β) receptor ALK5, which until now has only been associated with the biological functions of TGF-β1 to TGF-β3 proteins, mediates GDF11 signalling during embryogenesis.
Yuki Akieda - One of the best experts on this subject based on the ideXlab platform.
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Cell competition corrects noisy Wnt morphogen gradients to achieve robust Patterning in the zebrafish embryo
Nature Communications, 2019Co-Authors: Yuki Akieda, Shohei Ogamino, Hironobu Furuie, Shizuka Ishitani, Ryutaro Akiyoshi, Takamasa Masuda, Jumpei Nogami, Yasuyuki Ohkawa, Nobuyuki Shimizu, Tohru IshitaniAbstract:Gradients of morphogens such as Wnt provide instructive cues for cell identities during development. Here, the authors report that in the developing zebrafish embryo, cell competition and elimination of unfit cells are required for proper Wnt gradient formation.AbstractMorphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradients. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signalling gradient, which acts as a morphogen to establish embryonic Anterior-Posterior Patterning, identify that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin gradient formation and consequent Anterior-Posterior Patterning. Because this gradient controls Patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.
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Cell competition corrects noisy Wnt morphogen gradients to achieve robust Patterning in the zebrafish embryo
Nature communications, 2019Co-Authors: Yuki Akieda, Shohei Ogamino, Hironobu Furuie, Shizuka Ishitani, Ryutaro Akiyoshi, Takamasa Masuda, Jumpei Nogami, Yasuyuki Ohkawa, Nobuyuki Shimizu, Tohru IshitaniAbstract:Morphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradients. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signalling gradient, which acts as a morphogen to establish embryonic Anterior-Posterior Patterning, identify that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin gradient formation and consequent Anterior-Posterior Patterning. Because this gradient controls Patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.
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Cell competition corrects noisy Wnt morphogen gradients to achieve robust Patterning
2018Co-Authors: Yuki Akieda, Shohei Ogamino, Hironobu Furuie, Shizuka Ishitani, Ryutaro Akiyoshi, Takamasa Masuda, Jumpei Nogami, Yasuyuki Ohkawa, Nobuyuki Shimizu, Tohru IshitaniAbstract:Morphogen signaling forms an activity gradient and instructs cell identities in a signaling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signaling and consequent noisy morphogen gradient. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signaling-gradient, which acts as a morphogen to establish embryonic Anterior-Posterior Patterning, revealed that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the Wnt/β-catenin-gradient. Communication between the unfit and neighboring fit cells via cadherin proteins stimulates the apoptosis of the unfit cells by activating Smad signaling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin-gradient formation and consequent Anterior-Posterior Patterning. Because this gradient controls Patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.
Michael Schubert - One of the best experts on this subject based on the ideXlab platform.
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Retinoic acid and Wnt/β-catenin have complementary roles in anterior/posterior Patterning embryos of the basal chordate amphioxus
Developmental biology, 2009Co-Authors: Takayuki Onai, Michael Schubert, Nicholas D Holland, Hsiu-chin Lin, Demian Koop, Peter W. Osborne, Susana Álvarez, Rosana Alvarez, Linda Z HollandAbstract:Abstract A role for Wnt/β-catenin signaling in axial Patterning has been demonstrated in animals as basal as cnidarians, while roles in axial Patterning for retinoic acid (RA) probably evolved in the deuterostomes and may be chordate-specific. In vertebrates, these two pathways interact both directly and indirectly. To investigate the evolutionary origins of interactions between these two pathways, we manipulated Wnt/β-catenin and RA signaling in the basal chordate amphioxus during the gastrula stage, which is the RA-sensitive period for anterior/posterior (A/P) Patterning. The results show that Wnt/β-catenin and RA signaling have distinctly different roles in Patterning the A/P axis of the amphioxus gastrula. Wnt/β-catenin specifies the identity of the ends of the embryo (high Wnt = posterior; low Wnt = anterior) but not intervening positions. Thus, upregulation of Wnt/β-catenin signaling induces ectopic expression of posterior markers at the anterior tip of the embryo. In contrast, RA specifies position along the A/P axis, but not the identity of the ends of the embryo—increased RA signaling strongly affects the domains of Hox expression along the A/P axis but has little or no effect on the expression of either anterior or posterior markers. Although the two pathways may both influence such things as specification of neuronal identity, interactions between them in A/P Patterning appear to be minimal.
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a retinoic acid hox hierarchy controls both anterior posterior Patterning and neuronal specification in the developing central nervous system of the cephalochordate amphioxus
Developmental Biology, 2006Co-Authors: Michael Schubert, Nicholas D Holland, Vincent Laudet, Linda Z HollandAbstract:Retinoic acid (RA) mediates both anterior/posterior Patterning and neuronal specification in the vertebrate central nervous system (CNS). However, the molecular mechanisms downstream of RA are not well understood. To investigate these mechanisms, we used the invertebrate chordate amphioxus, in which the CNS, although containing only about 20,000 neurons in adults, like the vertebrate CNS, has a forebrain, midbrain, hindbrain, and spinal cord and is regionalized by RA-signaling. Here we show, first, that domains of genes with expression normally limited to diencephalon and midbrain are generally not affected by altered RA-signaling, second, that contrary to previous reports, not only Hox1, 3, and 4, but also Hox2 and Hox6 are collinearly expressed in the amphioxus CNS, and third, that collinear expression of all these Hox genes is controlled by RA-signaling. Finally, we show that Hox1 is involved in mediating both the role of RA-signaling in regionalization of the hindbrain and in specification of hindbrain motor neurons. Thus, morpholino knock-down of the single amphioxus Hox1 mimics the effects of treatments with an RA-antagonist. This analysis establishes RA-dependent regulation of collinear Hox expression as a feature common to the chordate CNS and indicates that the RA-Hox hierarchy functions both in proper anterior/posterior Patterning of the developing CNS and in specification of neuronal identity.
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A retinoic acid-Hox hierarchy controls both anterior/posterior Patterning and neuronal specification in the developing central nervous system of the cephalochordate amphioxus.
Developmental biology, 2006Co-Authors: Michael Schubert, Nicholas D Holland, Vincent Laudet, Linda Z HollandAbstract:Retinoic acid (RA) mediates both anterior/posterior Patterning and neuronal specification in the vertebrate central nervous system (CNS). However, the molecular mechanisms downstream of RA are not well understood. To investigate these mechanisms, we used the invertebrate chordate amphioxus, in which the CNS, although containing only about 20,000 neurons in adults, like the vertebrate CNS, has a forebrain, midbrain, hindbrain, and spinal cord and is regionalized by RA-signaling. Here we show, first, that domains of genes with expression normally limited to diencephalon and midbrain are generally not affected by altered RA-signaling, second, that contrary to previous reports, not only Hox1, 3, and 4, but also Hox2 and Hox6 are collinearly expressed in the amphioxus CNS, and third, that collinear expression of all these Hox genes is controlled by RA-signaling. Finally, we show that Hox1 is involved in mediating both the role of RA-signaling in regionalization of the hindbrain and in specification of hindbrain motor neurons. Thus, morpholino knock-down of the single amphioxus Hox1 mimics the effects of treatments with an RA-antagonist. This analysis establishes RA-dependent regulation of collinear Hox expression as a feature common to the chordate CNS and indicates that the RA-Hox hierarchy functions both in proper anterior/posterior Patterning of the developing CNS and in specification of neuronal identity.