The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Hiroki Kurihara - One of the best experts on this subject based on the ideXlab platform.
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temporal requirement of signaling cascade involving endothelin 1 endothelin receptor type a in Branchial Arch development
Mechanisms of Development, 2004Co-Authors: Shigetomo Fukuhara, Hiroki Kurihara, Yukiko Kurihara, Yuichiro Arima, Nobuhiro YamadaAbstract:Intercellular interactions within the Branchial Arch (BA) system is essential for craniofacial development. Endothelin-1 (ET-1), produced by the Branchial epithelium and core mesenchyme, acts on cranial neural crest-derived ectomesenchymcal cells expressing endothelin A receptor (ETAR) and regulates expression of crucial genes such as Dlx6, a member of distalless homeobox gene family, and its downstream target dHAND, a basic helix-loop-helix transcription factor. To investigate the role of ET-1 and subsequent signaling cascades in BA development, we examined when and how they activate dHAND and Dlx6 expression. ETAR blockade by BQ123 in mouse embryo culture has revealed that ET-1/ETAR signaling is critical for dHAND and Dlx6 expression in the mandibular Arch mesenchyme around embryonic day (E)8.75-E9.0 and becomes dispensable by E9.5. dHAND and Dlx6 expression after E9.5 was dependent on the presence of the epithelium, which was partly mediated by FGF-like signals. These findings indicate that ET-1/ETAR and subsequent epithelial signals are sequentially involved in BA development by maintaining dHAND and Dlx6 expression. Furthermore, discordance of dHAND and Dlx6 expression domains and heterogeneity with respect to dependency on ET-1 and FGF-like signals suggest that genetic hierArchy involving Dlx6 and dHAND is differently controlled among subdomains within the mandibular Arch.
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endothelin 1 regulates the dorsoventral Branchial Arch patterning in mice
Mechanisms of Development, 2004Co-Authors: Hidenori Ozeki, Yukiko Kurihara, Kazuo Tonami, Sanae Watatani, Hiroki KuriharaAbstract:Abstract Endothelin-1 (ET-1), a 21-amino acid peptide secreted by the epithelium and core mesenchyme in the Branchial Arches as well as vascular endothelium, is involved in craniofacial and cardiovascular development through endothelin receptor type-A (EdnrA) expressed in the neural crest-derived ectomesenchyme. Here we show that ET-1−/− mutant mice exhibit a homeotic-like transformation of the lower jaw to an upper jaw. Most of the maxillary Arch-derived components are duplicated and replaced mandibular Arch-derived structures, resulting in a mirror image of the upper and lower jaws in the ET-1−/− mutant. As for hyoid Arch-derivatives, the ventral structures are severely affected in comparison to the dorsal ones in the ET-1−/− mutant. Correspondingly, the expression of Dlx5 and Dlx6, Distalless-related homeobox genes determining the ventral identity of the anterior Branchial Arches, and of the mandibular marker gene Pitx1 is significantly downregulated in the ET-1−/− mutant, whereas the expression of Dlx2 and the maxillary marker gene Prx2 is unaffected or rather upregulated. These findings indicate that the ET-1/EdnrA signaling may contribute to the dorsoventral axis patterning of the Branchial Arch system as a mediator of the regional intercellular interactions.
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a signaling cascade involving endothelin 1 dhand and msx1 regulates development of neural crest derived Branchial Arch mesenchyme
Development, 1998Co-Authors: Tiffani Thomas, Eric N Olson, Hiroki Kurihara, Hiroyuki Yamagishi, Yukiko Kurihara, Yoshio Yazaki, Deepak SrivastavaAbstract:Numerous human syndromes are the result of abnormal cranial neural crest development. One group of such defects, referred to as CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, associated with chromosome 22 microdeletion) syndrome, exhibit craniofacial and cardiac defects resulting from abnormal development of the third and fourth neural crest-derived Branchial Arches and Branchial Arch arteries. Mice harboring a null mutation of the endothelin-1 gene (Edn1), which is expressed in the epithelial layer of the Branchial Arches and encodes for the endothelin-1 (ET-1) signaling peptide, have a phenotype similar to CATCH-22 syndrome with aortic Arch defects and craniofacial abnormalities. Here we show that the basic helix-loop-helix transcription factor, dHAND, is expressed in the mesenchyme underlying the Branchial Arch epithelium. Further, dHAND and the related gene, eHAND, are downregulated in the Branchial and aortic Arches of Edn1-null embryos. In mice homozygous null for the dHAND gene, the first and second Arches are hypoplastic secondary to programmed cell death and the third and fourth Arches fail to form. Molecular analysis revealed that most markers of the neural-crest-derived components of the Branchial Arch are expressed in dHAND-null embryos, suggesting normal migration of neural crest cells. However, expression of the homeobox gene, Msx1, was undetectable in the mesenchyme of dHAND-null Branchial Arches but unaffected in the limb bud, consistent with the separable regulatory elements of Msx1 previously described. Together, these data suggest a model in which epithelial secretion of ET-1 stimulates mesenchymal expression of dHAND, which regulates Msx1 expression in the growing, distal Branchial Arch. Complete disruption of this molecular pathway results in growth failure of the Branchial Arches from apoptosis, while partial disruption leads to defects of Branchial Arch derivatives, similar to those seen in CATCH-22 syndrome.
Yukiko Kurihara - One of the best experts on this subject based on the ideXlab platform.
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temporal requirement of signaling cascade involving endothelin 1 endothelin receptor type a in Branchial Arch development
Mechanisms of Development, 2004Co-Authors: Shigetomo Fukuhara, Hiroki Kurihara, Yukiko Kurihara, Yuichiro Arima, Nobuhiro YamadaAbstract:Intercellular interactions within the Branchial Arch (BA) system is essential for craniofacial development. Endothelin-1 (ET-1), produced by the Branchial epithelium and core mesenchyme, acts on cranial neural crest-derived ectomesenchymcal cells expressing endothelin A receptor (ETAR) and regulates expression of crucial genes such as Dlx6, a member of distalless homeobox gene family, and its downstream target dHAND, a basic helix-loop-helix transcription factor. To investigate the role of ET-1 and subsequent signaling cascades in BA development, we examined when and how they activate dHAND and Dlx6 expression. ETAR blockade by BQ123 in mouse embryo culture has revealed that ET-1/ETAR signaling is critical for dHAND and Dlx6 expression in the mandibular Arch mesenchyme around embryonic day (E)8.75-E9.0 and becomes dispensable by E9.5. dHAND and Dlx6 expression after E9.5 was dependent on the presence of the epithelium, which was partly mediated by FGF-like signals. These findings indicate that ET-1/ETAR and subsequent epithelial signals are sequentially involved in BA development by maintaining dHAND and Dlx6 expression. Furthermore, discordance of dHAND and Dlx6 expression domains and heterogeneity with respect to dependency on ET-1 and FGF-like signals suggest that genetic hierArchy involving Dlx6 and dHAND is differently controlled among subdomains within the mandibular Arch.
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endothelin 1 regulates the dorsoventral Branchial Arch patterning in mice
Mechanisms of Development, 2004Co-Authors: Hidenori Ozeki, Yukiko Kurihara, Kazuo Tonami, Sanae Watatani, Hiroki KuriharaAbstract:Abstract Endothelin-1 (ET-1), a 21-amino acid peptide secreted by the epithelium and core mesenchyme in the Branchial Arches as well as vascular endothelium, is involved in craniofacial and cardiovascular development through endothelin receptor type-A (EdnrA) expressed in the neural crest-derived ectomesenchyme. Here we show that ET-1−/− mutant mice exhibit a homeotic-like transformation of the lower jaw to an upper jaw. Most of the maxillary Arch-derived components are duplicated and replaced mandibular Arch-derived structures, resulting in a mirror image of the upper and lower jaws in the ET-1−/− mutant. As for hyoid Arch-derivatives, the ventral structures are severely affected in comparison to the dorsal ones in the ET-1−/− mutant. Correspondingly, the expression of Dlx5 and Dlx6, Distalless-related homeobox genes determining the ventral identity of the anterior Branchial Arches, and of the mandibular marker gene Pitx1 is significantly downregulated in the ET-1−/− mutant, whereas the expression of Dlx2 and the maxillary marker gene Prx2 is unaffected or rather upregulated. These findings indicate that the ET-1/EdnrA signaling may contribute to the dorsoventral axis patterning of the Branchial Arch system as a mediator of the regional intercellular interactions.
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a signaling cascade involving endothelin 1 dhand and msx1 regulates development of neural crest derived Branchial Arch mesenchyme
Development, 1998Co-Authors: Tiffani Thomas, Eric N Olson, Hiroki Kurihara, Hiroyuki Yamagishi, Yukiko Kurihara, Yoshio Yazaki, Deepak SrivastavaAbstract:Numerous human syndromes are the result of abnormal cranial neural crest development. One group of such defects, referred to as CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, associated with chromosome 22 microdeletion) syndrome, exhibit craniofacial and cardiac defects resulting from abnormal development of the third and fourth neural crest-derived Branchial Arches and Branchial Arch arteries. Mice harboring a null mutation of the endothelin-1 gene (Edn1), which is expressed in the epithelial layer of the Branchial Arches and encodes for the endothelin-1 (ET-1) signaling peptide, have a phenotype similar to CATCH-22 syndrome with aortic Arch defects and craniofacial abnormalities. Here we show that the basic helix-loop-helix transcription factor, dHAND, is expressed in the mesenchyme underlying the Branchial Arch epithelium. Further, dHAND and the related gene, eHAND, are downregulated in the Branchial and aortic Arches of Edn1-null embryos. In mice homozygous null for the dHAND gene, the first and second Arches are hypoplastic secondary to programmed cell death and the third and fourth Arches fail to form. Molecular analysis revealed that most markers of the neural-crest-derived components of the Branchial Arch are expressed in dHAND-null embryos, suggesting normal migration of neural crest cells. However, expression of the homeobox gene, Msx1, was undetectable in the mesenchyme of dHAND-null Branchial Arches but unaffected in the limb bud, consistent with the separable regulatory elements of Msx1 previously described. Together, these data suggest a model in which epithelial secretion of ET-1 stimulates mesenchymal expression of dHAND, which regulates Msx1 expression in the growing, distal Branchial Arch. Complete disruption of this molecular pathway results in growth failure of the Branchial Arches from apoptosis, while partial disruption leads to defects of Branchial Arch derivatives, similar to those seen in CATCH-22 syndrome.
Robert M Greene - One of the best experts on this subject based on the ideXlab platform.
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determinants of orofacial clefting ii effects of 5 aza 2 deoxycytidine on gene methylation during development of the first Branchial Arch
Reproductive Toxicology, 2017Co-Authors: Ratnam S Seelan, Partha Mukhopadhyay, Dennis R Warner, Irina A Smolenkova, Michele M Pisano, Robert M GreeneAbstract:Abstract Defects in development of the secondary palate, which arise from the embryonic first Branchial Arch (1-BA), can cause cleft palate (CP). Administration of 5-Aza-2′-deoxycytidine (AzaD), a demethylating agent, to pregnant mice on gestational day 9.5 resulted in complete penetrance of CP in fetuses. Several genes critical for normal palatogenesis were found to be upregulated in 1-BA, 12 h after AzaD exposure. MethylCap-Seq (MCS) analysis identified several differentially methylated regions (DMRs) in DNA extracted from AzaD-exposed 1-BAs. Hypomethylated DMRs did not correlate with the upregulation of genes in AzaD-exposed 1-BAs. However, most DMRs were associated with endogenous retroviral elements. Expression analyses suggested that interferon signaling was activated in AzaD-exposed 1-BAs. Our data, thus, suggest that a 12-h in utero AzaD exposure demethylates and activates endogenous retroviral elements in the 1-BA, thereby triggering an interferon-mediated response. This may result in the dysregulation of key signaling pathways during palatogenesis, causing CP.
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determinants of orofacial clefting i effects of 5 aza 2 deoxycytidine on cellular processes and gene expression during development of the first Branchial Arch
Reproductive Toxicology, 2017Co-Authors: Partha Mukhopadhyay, Ratnam S Seelan, Dennis R Warner, Irina A Smolenkova, Michele M Pisano, Francine Rezzoug, Guy N Brock, Robert M GreeneAbstract:In this study, we identify gene targets and cellular events mediating the teratogenic action(s) of 5-Aza-2'-deoxycytidine (AzaD), an inhibitor of DNA methylation, on secondary palate development. Exposure of pregnant mice (on gestation day (GD) 9.5) to AzaD for 12h resulted in the complete penetrance of cleft palate (CP) in fetuses. Analysis of cells of the embryonic first Branchial Arch (1-BA), in fetuses exposed to AzaD, revealed: 1) significant alteration in expression of genes encoding several morphogenetic factors, cell cycle inhibitors and regulators of apoptosis; 2) a decrease in cell proliferation; and, 3) an increase in apoptosis. Pyrosequencing of selected genes, displaying pronounced differential expression in AzaD-exposed 1-BAs, failed to reveal significant alterations in CpG methylation levels in their putative promoters or gene bodies. CpG methylation analysis suggested that the effects of AzaD on gene expression were likely indirect.
Eric N Olson - One of the best experts on this subject based on the ideXlab platform.
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requirement of myocardin related transcription factor b for remodeling of Branchial Arch arteries and smooth muscle differentiation
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Jiyeon Oh, James A Richardson, Eric N OlsonAbstract:Myocardin and the myocardin-related transcription factors (MRTFs) A and B act as coactivators for serum response factor, which plays a key role in cardiovascular development. To determine the functions of MRTF-B in vivo, we generated MRTF-B mutant mice by targeted inactivation of the MRTF-B gene. We show that mice homozygous for an MRTF-B loss-of-function mutation die during mid-gestation from a spectrum of cardiovascular defects that includes abnormal patterning of the Branchial Arch arteries, double-outlet right ventricle, ventricular septal defects, and thin-walled myocardium. These abnormalities are accompanied by a failure in differentiation of smooth muscle cells within the Branchial Arch arteries, which are derived from the neural crest. The phenotype of MRTF-B mutant mice is distinct from that of mice lacking myocardin, revealing unique roles for these serum response factor coactivators in the development of different subsets of smooth muscle cells in vivo.
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targeted deletion of a Branchial Arch specific enhancer reveals a role of dhand in craniofacial development
Development, 2003Co-Authors: Hiromi Yanagisawa, James A Richardson, David E Clouthier, Jeroen Charite, Eric N OlsonAbstract:The basic helix-loop-helix transcription factor dHAND is expressed in the mesenchyme of Branchial Arches and the developing heart. Mice homozygous for a dHAND (Hand2) null mutation die early in embryogenesis from cardiac abnormalities, precluding analysis of the potential role of dHAND in Branchial Arch development. Two independent enhancers control expression of dHAND in the heart and Branchial Arches. Endothelin-1 (ET-1) signaling regulates the Branchial Arch enhancer and is required for dHAND expression in the Branchial Arches. To determine the potential role of dHAND in Branchial Arch development and to assess the role of the ET-1-dependent enhancer in dHAND regulation in vivo, we deleted this enhancer by homologous recombination. Mice lacking the dHAND Branchial Arch enhancer died perinatally and exhibited a spectrum of craniofacial defects that included cleft palate, mandibular hypoplasia and cartilage malformations. Expression of dHAND was abolished in the ventolateral regions of the first and second Branchial Arches in these mutant mice, but expression was retained in a ventral domain where the related transcription factor eHAND is expressed. We conclude that dHAND plays an essential role in patterning and development of skeletal elements derived from the first and second Branchial Arches and that there are heterogeneous populations of cells in the Branchial Arches that rely on different cis-regulatory elements for activation of dHAND transcription.
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role of dlx6 in regulation of an endothelin 1 dependent dhand Branchial Arch enhancer
Genes & Development, 2001Co-Authors: Jeroen Charite, James A Richardson, David E Clouthier, David G Mcfadden, Giorgio R Merlo, Giovanni Levi, Masashi Yanagisawa, Eric N OlsonAbstract:Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the Branchial Arch neural crest. The basic helix–loop–helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the Branchial Arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the Branchial Arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for Branchial Arch expression. By comparing protein binding to these sites in Branchial Arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in Branchial Arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis.
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a signaling cascade involving endothelin 1 dhand and msx1 regulates development of neural crest derived Branchial Arch mesenchyme
Development, 1998Co-Authors: Tiffani Thomas, Eric N Olson, Hiroki Kurihara, Hiroyuki Yamagishi, Yukiko Kurihara, Yoshio Yazaki, Deepak SrivastavaAbstract:Numerous human syndromes are the result of abnormal cranial neural crest development. One group of such defects, referred to as CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, associated with chromosome 22 microdeletion) syndrome, exhibit craniofacial and cardiac defects resulting from abnormal development of the third and fourth neural crest-derived Branchial Arches and Branchial Arch arteries. Mice harboring a null mutation of the endothelin-1 gene (Edn1), which is expressed in the epithelial layer of the Branchial Arches and encodes for the endothelin-1 (ET-1) signaling peptide, have a phenotype similar to CATCH-22 syndrome with aortic Arch defects and craniofacial abnormalities. Here we show that the basic helix-loop-helix transcription factor, dHAND, is expressed in the mesenchyme underlying the Branchial Arch epithelium. Further, dHAND and the related gene, eHAND, are downregulated in the Branchial and aortic Arches of Edn1-null embryos. In mice homozygous null for the dHAND gene, the first and second Arches are hypoplastic secondary to programmed cell death and the third and fourth Arches fail to form. Molecular analysis revealed that most markers of the neural-crest-derived components of the Branchial Arch are expressed in dHAND-null embryos, suggesting normal migration of neural crest cells. However, expression of the homeobox gene, Msx1, was undetectable in the mesenchyme of dHAND-null Branchial Arches but unaffected in the limb bud, consistent with the separable regulatory elements of Msx1 previously described. Together, these data suggest a model in which epithelial secretion of ET-1 stimulates mesenchymal expression of dHAND, which regulates Msx1 expression in the growing, distal Branchial Arch. Complete disruption of this molecular pathway results in growth failure of the Branchial Arches from apoptosis, while partial disruption leads to defects of Branchial Arch derivatives, similar to those seen in CATCH-22 syndrome.
Deepak Srivastava - One of the best experts on this subject based on the ideXlab platform.
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conservation of sequence and expression of xenopus and zebrafish dhand during cardiac Branchial Arch and lateral mesoderm development
Mechanisms of Development, 2000Co-Authors: Stephanie Angelo, Jamie L Lohr, Kyu H Lee, Baruch S Ticho, Roger E Breitbart, Sandra Hill, Joseph H Yost, Deepak SrivastavaAbstract:dHAND and eHAND are related basic helix-loop-helix transcription factors that are expressed in the cardiac mesoderm and in numerous neural crest-derived cell types in chick and mouse. To better understand the evolutionary development of overlapping expression and function of the HAND genes during embryogenesis, we cloned the zebrafish and Xenopus orthologues. Comparison of dHAND sequences in zebrafish, Xenopus, chick, mouse and human demonstrated conservation throughout the protein. Expression of dHAND in zebrafish was seen in the earliest precursors of all lateral mesoderm at early gastrulation stages. At neurula and later stages, dHAND expression was observed in lateral precardiac mesoderm, Branchial Arch neural crest derivatives and posterior lateral mesoderm. At looping heart stages, cardiac dHAND expression remained generalized with no apparent regionalization. Interestingly, no eHAND orthologue was found in zebrafish. In Xenopus, dHAND and eHAND were co-expressed in the cardiac mesoderm without the segmental restriction seen in mice. Xenopus dHAND and eHAND were also expressed bilaterally in the lateral mesoderm without any left-right asymmetry. Within the Branchial Arches, XdHAND was expressed in a broader domain than XeHAND, similar to their mouse counterparts. Together, these data demonstrate conservation of HAND structure and expression across species.
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a signaling cascade involving endothelin 1 dhand and msx1 regulates development of neural crest derived Branchial Arch mesenchyme
Development, 1998Co-Authors: Tiffani Thomas, Eric N Olson, Hiroki Kurihara, Hiroyuki Yamagishi, Yukiko Kurihara, Yoshio Yazaki, Deepak SrivastavaAbstract:Numerous human syndromes are the result of abnormal cranial neural crest development. One group of such defects, referred to as CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, associated with chromosome 22 microdeletion) syndrome, exhibit craniofacial and cardiac defects resulting from abnormal development of the third and fourth neural crest-derived Branchial Arches and Branchial Arch arteries. Mice harboring a null mutation of the endothelin-1 gene (Edn1), which is expressed in the epithelial layer of the Branchial Arches and encodes for the endothelin-1 (ET-1) signaling peptide, have a phenotype similar to CATCH-22 syndrome with aortic Arch defects and craniofacial abnormalities. Here we show that the basic helix-loop-helix transcription factor, dHAND, is expressed in the mesenchyme underlying the Branchial Arch epithelium. Further, dHAND and the related gene, eHAND, are downregulated in the Branchial and aortic Arches of Edn1-null embryos. In mice homozygous null for the dHAND gene, the first and second Arches are hypoplastic secondary to programmed cell death and the third and fourth Arches fail to form. Molecular analysis revealed that most markers of the neural-crest-derived components of the Branchial Arch are expressed in dHAND-null embryos, suggesting normal migration of neural crest cells. However, expression of the homeobox gene, Msx1, was undetectable in the mesenchyme of dHAND-null Branchial Arches but unaffected in the limb bud, consistent with the separable regulatory elements of Msx1 previously described. Together, these data suggest a model in which epithelial secretion of ET-1 stimulates mesenchymal expression of dHAND, which regulates Msx1 expression in the growing, distal Branchial Arch. Complete disruption of this molecular pathway results in growth failure of the Branchial Arches from apoptosis, while partial disruption leads to defects of Branchial Arch derivatives, similar to those seen in CATCH-22 syndrome.