The Experts below are selected from a list of 2442 Experts worldwide ranked by ideXlab platform
Anne M Moon - One of the best experts on this subject based on the ideXlab platform.
-
Gng5−/− mutants fail to form the cardiac outflow tract and right ventricle and have severely hypoplastic Pharyngeal Arches.
2014Co-Authors: Anne M Moon, Anna M. Stauffer, William F. Schwindinger, Kathy Sheridan, Ashley Firment, Janet D. RobishawAbstract:Panels A–D images of e8.5 whole mount wild type and mutant embryos. By comparing the left lateral (A, C) and ventral (B, D) views of intact wild type and Gng5−/− embryos, respectively, the unlooped heart tube is clearly evident (B, D). Panels E–H, images of e9.5 wild type and mutant embryos. The left parasagittal section from a control embryo shows the inflow tract and left side of common atrium, endocardial cushion in the atrioventricular canal, and left ventricle (E). The red arrowheads mark the first Pharyngeal Arch, also labeled 1. The midline section shows the outflow tract connecting to aortic sac in the second Pharyngeal Arch (bracket), right ventricle, the right portion of the common atrium, and the sinus venosus in the control embryo (F). The left parasagittal section of a Gng5−/− mutant shows severely hypoplastic but vascularized first Pharyngeal Arch (red arrowhead), dilated heart tube with atrial chamber caudal to ventricle, narrow inflow, and paucity of cells in the Pharyngeal mesoderm (G). The midline section shows the unlooped, dilated heart tube and no outflow tract; cardiac chamber opens directly into dilated aortic sac (bracket) in a Gng5−/− embryo (H). TB, tail bud; HF, head fold; OFT, outflow tract; RV, right ventricle; LV, left ventricle; A, atrium V, ventricle; EC, endocardial cushion; SV, sinus venosus.
-
role of mesodermal fgf8 and fgf10 overlaps in the development of the arterial pole of the heart and Pharyngeal Arch arteries
Circulation Research, 2010Co-Authors: Yusuke Watanabe, Anne M Moon, Sachiko Miyagawatomita, Stephane D Vincent, Robert G Kelly, Margaret BuckinghamAbstract:Rationale: The genes encoding fibroblast growth factor (FGF) 8 and 10 are expressed in the anterior part of the second heart field that constitutes a population of cardiac progenitor cells contributing to the arterial pole of the heart. Previous studies of hypomorphic and conditional Fgf8 mutants show disrupted outflow tract (OFT) and right ventricle (RV) development, whereas Fgf10 mutants do not have detectable OFT defects. Objectives: Our aim was to investigate functional overlap between Fgf8 and Fgf10 during formation of the arterial pole. Methods and Results: We generated mesodermal Fgf8; Fgf10 compound mutants with MesP1Cre . The OFT/RV morphology in these mutants was affected with variable penetrance; however, the incidence of embryos with severely affected OFT/RV morphology was significantly increased in response to decreasing Fgf8 and Fgf10 gene dosage. Fgf8 expression in the Pharyngeal Arch ectoderm is important for development of the Pharyngeal Arch arteries and their derivatives. We now show that Fgf8 deletion in the mesoderm alone leads to Pharyngeal Arch artery phenotypes and that these vascular phenotypes are exacerbated by loss of Fgf10 function in the mesodermal core of the Arches. Conclusions: These results show functional overlap of FGF8 and FGF10 signaling from second heart field mesoderm during development of the OFT/RV, and from Pharyngeal Arch mesoderm during Pharyngeal Arch artery formation, highlighting the sensitivity of these key aspects of cardiovascular development to FGF dosage.
-
ablation of specific expression domains reveals discrete functions of ectoderm and endoderm derived fgf8 during cardiovascular and Pharyngeal development
Development, 2003Co-Authors: Timothy L Macatee, Deborah U Frank, Benjamin P Hammond, Benjamin R Arenkiel, Lily Francis, Anne M MoonAbstract:Fibroblast growth factor 8 (Fgf8) is expressed in many domains of the developing embryo. Globally decreased FGF8 signaling during murine embryogenesis results in a hypomorphic phenotype with a constellation of heart, outflow tract, great vessel and Pharyngeal gland defects that phenocopies human deletion 22q11 syndromes, such as DiGeorge. We postulate that these Fgf8 hypomorphic phenotypes result from disruption of local FGF8 signaling from Pharyngeal Arch epithelia to mesenchymal cells populating and migrating through the third and fourth Pharyngeal Arches. To test our hypothesis, and to determine whether the Pharyngeal ectoderm and endoderm Fgf8 expression domains have discrete functional roles, we performed conditional mutagenesis of Fgf8 using novel Crerecombinase drivers to achieve domain-specific ablation of Fgf8 gene function in the Pharyngeal Arch ectoderm and endoderm. Remarkably, ablating FGF8 protein in the Pharyngeal Arch ectoderm causes failure of formation of the fourth Pharyngeal Arch artery that results in aortic Arch and subclavian artery anomalies in 95% of mutants; these defects recapitulate the spectrum and frequency of vascular defects reported in Fgf8 hypomorphs. Surprisingly, no cardiac, outflow tract or glandular defects were found in ectodermal-domain mutants, indicating that ectodermally derived FGF8 has essential roles during Pharyngeal Arch vascular development distinct from those in cardiac, outflow tract and Pharyngeal gland morphogenesis. By contrast, ablation of FGF8 in the third and fourth Pharyngeal endoderm and ectoderm caused glandular defects and bicuspid aortic valve, which indicates that the FGF8 endodermal domain has discrete roles in Pharyngeal and valvar development. These results support our hypotheses that local FGF8 signaling from the Pharyngeal epithelia is required for Pharyngeal vascular and glandular development, and that the Pharyngeal ectodermal and endodermal domains of FGF8 have separate functions.
-
an fgf8 mouse mutant phenocopies human 22q11 deletion syndrome
Development, 2002Co-Authors: Deborah U Frank, Lori Fotheringham, Judson A Brewer, Louis J Muglia, Martin Tristanifirouzi, Mario R Capecchi, Anne M MoonAbstract:Deletion of chromosome 22q11, the most common microdeletion detected in humans, is associated with a life-threatening array of birth defects. Although 90% of affected individuals share the same three megabase deletion, their phenotype is highly variable and includes craniofacial and cardiovascular anomalies, hypoplasia or aplasia of the thymus with associated deficiency of T cells, hypocalcemia with hypoplasia or aplasia of the parathyroids, and a variety of central nervous system abnormalities. Because ablation of neural crest in chicks produces many features of the deletion 22q11 syndrome, it has been proposed that haploinsufficiency in this region impacts neural crest function during cardiac and Pharyngeal Arch development. Few factors required for migration, survival, proliferation and subsequent differentiation of Pharyngeal Arch neural crest and mesoderm-derived mesenchyme into their respective cardiovascular, musculoskeletal, and glandular derivatives have been identified. However, the importance of epithelial-mesenchymal interactions and Pharyngeal endoderm function is becoming increasingly clear. Fibroblast growth factor 8 is a signaling molecule expressed in the ectoderm and endoderm of the developing Pharyngeal Arches and known to play an important role in survival and patterning of first Arch tissues. We demonstrate a dosage-sensitive requirement for FGF8 during development of Pharyngeal Arch, Pharyngeal pouch and neural crest-derived tissues. We show that FGF8 deficient embryos have lethal malformations of the cardiac outflow tract, great vessels and heart due, at least in part, to failure to form the fourth Pharyngeal Arch arteries, altered expression of Fgf10 in the Pharyngeal mesenchyme, and abnormal apoptosis in Pharyngeal and cardiac neural crest. The Fgf8 mutants described herein display the complete array of cardiovascular, glandular and craniofacial phenotypes seen in human deletion 22q11 syndromes. This represents the first single gene disruption outside the typically deleted region of human chromosome 22 to fully recapitulate the deletion 22q11 phenotype. FGF8 may operate directly in molecular pathways affected by deletions in 22q11 or function in parallel pathways required for normal development of Pharyngeal Arch and neural crest-derived tissues. In either case, Fgf8 may function as a modifier of the 22q11 deletion and contribute to the phenotypic variability of this syndrome.
-
DEVELOPMENT AND DISEASE An Fgf8 mouse mutant phenocopies human 22q11 deletion syndrome
2002Co-Authors: Deborah U Frank, Judson A Brewer, Louis J Muglia, Mario R Capecchi, Lori K. Fotheringham, Martin Tristani-firouzi, Anne M MoonAbstract:microdeletion detected in humans, is associated with a lifethreatening array of birth defects. Although 90 % of affected individuals share the same three megabase deletion, their phenotype is highly variable and includes craniofacial and cardiovascular anomalies, hypoplasia or aplasia of the thymus with associated deficiency of T cells, hypocalcemia with hypoplasia or aplasia of the parathyroids, and a variety of central nervous system abnormalities. Because ablation of neural crest in chicks produces many features of the deletion 22q11 syndrome, it has been proposed that haploinsufficiency in this region impacts neural crest function during cardiac and Pharyngeal Arch development. Few factors required for migration, survival, proliferation and subsequent differentiation of Pharyngeal Arch neural crest an
Deepak Srivastava - One of the best experts on this subject based on the ideXlab platform.
-
the neural crest enriched microrna mir 452 regulates epithelial mesenchymal signaling in the first Pharyngeal Arch
Development, 2010Co-Authors: Neil T Sheehy, Kathryn N Ivey, Kimberly R Cordes, Mark P White, Deepak SrivastavaAbstract:Neural crest cells (NCCs) are a subset of multipotent, migratory stem cells that populate a large number of tissues during development and are important for craniofacial and cardiac morphogenesis. Although microRNAs (miRNAs) have emerged as important regulators of development and disease, little is known about their role in NCC development. Here, we show that loss of miRNA biogenesis by NCC-specific disruption of murine Dicer results in embryos lacking craniofacial cartilaginous structures, cardiac outflow tract septation and thymic and dorsal root ganglia development. Dicer mutant embryos had reduced expression of Dlx2, a transcriptional regulator of Pharyngeal Arch development, in the first Pharyngeal Arch (PA1). miR-452 was enriched in NCCs, was sufficient to rescue Dlx2 expression in Dicer mutant Pharyngeal Arches, and regulated non-cell-autonomous signaling involving Wnt5a, Shh and Fgf8 that converged on Dlx2 regulation in PA1. Correspondingly, knockdown of miR-452 in vivo decreased Dlx2 expression in the mandibular component of PA1, leading to craniofacial defects. These results suggest that post-transcriptional regulation by miRNAs is required for differentiation of NCC-derived tissues and that miR-452 is involved in epithelial-mesenchymal signaling in the Pharyngeal Arch.
-
Sonic Hedgehog Is Essential for First Pharyngeal Arch Development
Pediatric Research, 2006Co-Authors: Chihiro Yamagishi, Takatoshi Tsuchihashi, Hiroyuki Yamagishi, Jun Maeda, Kathryn Ivey, Deepak SrivastavaAbstract:The secreted protein sonic hedgehog (Shh) is essential for normal development of many organs. Targeted disruption of Shh in mouse leads to near complete absence of craniofacial skeletal elements at birth, and mutation of SHH in human causes holoprosencephaly (HPE), frequently associated with defects of derivatives of Pharyngeal Arches. To investigate the role of Shh signaling in early Pharyngeal Arch development, we analyzed Shh mutant embryos using molecular markers and found that the first Pharyngeal Arch (PA1) was specifically hypoplastic and fused in the midline, and remaining Arches were well formed at embryonic day (E) 9.5. Molecular analyses using specific markers suggested that the growth of the maxillary Arch and proximal mandibular Arch was severely defective in Shh -null PA1, whereas the distal mandibular Arch was less affected. TUNEL assay revealed an increase in the number of apoptotic signals in PA1 of Shh mutant embryos. Ectodermal expression of fibroblast growth factor ( Fgf )-8, a cell survival factor for Pharyngeal Arch mesenchyme, was down-regulated in the PA1 of Shh mutants. Consistent with this observation, downstream transcriptional targets of Fgf8 signaling in neural crest–derived mesenchyme, including Barx1 , goosecoid , and Dlx2 , were also down-regulated in Shh -null PA1. These results demonstrate that epithelial-mesenchymal signaling and transcriptional events coordinated by Shh, partly via Fgf8, is essential for cell survival and tissue outgrowth of the developing PA1.
-
articles sonic hedgehog is essential for first Pharyngeal Arch development
2006Co-Authors: Chihiro Yamagishi, Takatoshi Tsuchihashi, Hiroyuki Yamagishi, Jun Maeda, Kathryn N Ivey, Deepak SrivastavaAbstract:The secreted protein sonic hedgehog (Shh) is essential for normal development of many organs. Targeted disruption of Shh in mouse leads to near complete absence of craniofacial skeletal elements at birth, and mutation of SHH in human causes holoprosen- cephaly (HPE), frequently associated with defects of derivatives of Pharyngeal Arches. To investigate the role of Shh signaling in early Pharyngeal Arch development, we analyzed Shh mutant embryos using molecular markers and found that the first Pharyngeal Arch (PA1) was specifically hypoplastic and fused in the midline, and remaining Arches were well formed at embryonic day (E) 9.5. Molecular analyses using specific markers suggested that the growth of the maxillary Arch and proximal mandibular Arch was severely defective in Shh-null PA1, whereas the distal mandibular Arch was less affected. TUNEL assay revealed an increase in the number of apoptotic signals in PA1 of Shh mutant embryos. Ectodermal expression of fibroblast growth factor (Fgf)-8, a cell survival factor for Pharyngeal Arch mesenchyme, was down- regulated in the PA1 of Shh mutants. Consistent with this obser- vation, downstream transcriptional targets of Fgf8 signaling in neural crest-derived mesenchyme, including Barx1, goosecoid, and Dlx2, were also down-regulated in Shh-null PA1. These results demonstrate that epithelial-mesenchymal signaling and transcriptional events coordinated by Shh, partly via Fgf8, is essential for cell survival and tissue outgrowth of the developing PA1. (Pediatr Res 59: 349-354, 2006)
-
loss of apaf 1 leads to partial rescue of the hand2 null phenotype
Developmental Biology, 2005Co-Authors: Aparna R Aiyer, Narimon Honarpour, Joachim Herz, Deepak SrivastavaAbstract:HAND2 is an essential transcription factor for cardiac, Pharyngeal Arch, and limb development. Apoptosis in the HAND2-null embryo causes hypoplasia of the right ventricle and Pharyngeal Arches leading to lethality by embryonic day (E)10.0 from heart failure. In order to investigate the role of apoptosis in inducing the HAND2-null phenotype, we generated mouse embryos lacking both HAND2 and Apaf-1, a central downstream mediator of mitochondrial damage-induced apoptosis. In contrast to HAND2 / embryos, HAND2 / Apaf-1 / embryos at E10.5–11.0 had well-developed Pharyngeal Arches, aortic Arch arteries, and no signs of cardiac failure. TUNEL analysis through Pharyngeal Arches of HAND2 / Apaf-1 / embryos revealed decreased apoptosis and the embryos had clearly patent aortic Arch arteries. However, ventricular hypoplasia and cell death were unchanged in these animals compared to HAND2 / embryos, resulting in growth arrest at E11.0. Our study suggests that loss of HAND2 in the Pharyngeal Arch mesenchyme leads to apoptosis in an Apaf-1-dependent fashion and that, while loss of aortic Arch integrity contributes to the early lethality, the ventricular defects are independent of Arch development.
-
gαq and gα11 proteins mediate endothelin 1 signaling in neural crest derived Pharyngeal Arch mesenchyme
Developmental Biology, 2003Co-Authors: Kathryn N Ivey, Deepak Srivastava, Brandi Tyson, Pallavi Ukidwe, David G Mcfadden, Giovanni Levi, Eric N Olson, Thomas M WilkieAbstract:Endothelin-A (ET(A)) is a G-protein-coupled receptor expressed in the neural crest-derived mesenchyme of the Pharyngeal Arches during craniofacial development. Targeted deletion of the ET(A) receptor or its ligand endothelin-1 (ET-1) causes cleft palate and hypoplasia of the mandible, otic cup, and tympanic ring. Previously we showed that Galpha(q)/Galpha(11)-null mice die around E11.0, whereas Galpha(q)((-/-))Galpha(11)((+/-)) mice survive to birth with hypomorphic phenotypes similar to, but less severe than, ET(A) or ET-1-null mice. To determine whether ET-1 signaling is transduced by Galpha(q)/Galpha(11) proteins, we examined the expression patterns of several ET-1 dependent and independent transcription factors in Galpha(q)/Galpha(11)-deficient embryos. Expression of genes encoding the ET-1-dependent transcription factors Dlx3, Dlx6, dHAND, and eHAND was specifically downregulated in the Pharyngeal Arches of Galpha(q)/Galpha(11)-deficient mice. In contrast, Pharyngeal Arch expression of the homeobox gene Msx1, which is not regulated by ET-1 signaling, was maintained in these embryos. We conclude that the Galpha(q) and Galpha(11) proteins serve as the intracellular mediators of ET-1 signaling in the Pharyngeal Arch mesenchyme.
Deborah U Frank - One of the best experts on this subject based on the ideXlab platform.
-
ablation of specific expression domains reveals discrete functions of ectoderm and endoderm derived fgf8 during cardiovascular and Pharyngeal development
Development, 2003Co-Authors: Timothy L Macatee, Deborah U Frank, Benjamin P Hammond, Benjamin R Arenkiel, Lily Francis, Anne M MoonAbstract:Fibroblast growth factor 8 (Fgf8) is expressed in many domains of the developing embryo. Globally decreased FGF8 signaling during murine embryogenesis results in a hypomorphic phenotype with a constellation of heart, outflow tract, great vessel and Pharyngeal gland defects that phenocopies human deletion 22q11 syndromes, such as DiGeorge. We postulate that these Fgf8 hypomorphic phenotypes result from disruption of local FGF8 signaling from Pharyngeal Arch epithelia to mesenchymal cells populating and migrating through the third and fourth Pharyngeal Arches. To test our hypothesis, and to determine whether the Pharyngeal ectoderm and endoderm Fgf8 expression domains have discrete functional roles, we performed conditional mutagenesis of Fgf8 using novel Crerecombinase drivers to achieve domain-specific ablation of Fgf8 gene function in the Pharyngeal Arch ectoderm and endoderm. Remarkably, ablating FGF8 protein in the Pharyngeal Arch ectoderm causes failure of formation of the fourth Pharyngeal Arch artery that results in aortic Arch and subclavian artery anomalies in 95% of mutants; these defects recapitulate the spectrum and frequency of vascular defects reported in Fgf8 hypomorphs. Surprisingly, no cardiac, outflow tract or glandular defects were found in ectodermal-domain mutants, indicating that ectodermally derived FGF8 has essential roles during Pharyngeal Arch vascular development distinct from those in cardiac, outflow tract and Pharyngeal gland morphogenesis. By contrast, ablation of FGF8 in the third and fourth Pharyngeal endoderm and ectoderm caused glandular defects and bicuspid aortic valve, which indicates that the FGF8 endodermal domain has discrete roles in Pharyngeal and valvar development. These results support our hypotheses that local FGF8 signaling from the Pharyngeal epithelia is required for Pharyngeal vascular and glandular development, and that the Pharyngeal ectodermal and endodermal domains of FGF8 have separate functions.
-
an fgf8 mouse mutant phenocopies human 22q11 deletion syndrome
Development, 2002Co-Authors: Deborah U Frank, Lori Fotheringham, Judson A Brewer, Louis J Muglia, Martin Tristanifirouzi, Mario R Capecchi, Anne M MoonAbstract:Deletion of chromosome 22q11, the most common microdeletion detected in humans, is associated with a life-threatening array of birth defects. Although 90% of affected individuals share the same three megabase deletion, their phenotype is highly variable and includes craniofacial and cardiovascular anomalies, hypoplasia or aplasia of the thymus with associated deficiency of T cells, hypocalcemia with hypoplasia or aplasia of the parathyroids, and a variety of central nervous system abnormalities. Because ablation of neural crest in chicks produces many features of the deletion 22q11 syndrome, it has been proposed that haploinsufficiency in this region impacts neural crest function during cardiac and Pharyngeal Arch development. Few factors required for migration, survival, proliferation and subsequent differentiation of Pharyngeal Arch neural crest and mesoderm-derived mesenchyme into their respective cardiovascular, musculoskeletal, and glandular derivatives have been identified. However, the importance of epithelial-mesenchymal interactions and Pharyngeal endoderm function is becoming increasingly clear. Fibroblast growth factor 8 is a signaling molecule expressed in the ectoderm and endoderm of the developing Pharyngeal Arches and known to play an important role in survival and patterning of first Arch tissues. We demonstrate a dosage-sensitive requirement for FGF8 during development of Pharyngeal Arch, Pharyngeal pouch and neural crest-derived tissues. We show that FGF8 deficient embryos have lethal malformations of the cardiac outflow tract, great vessels and heart due, at least in part, to failure to form the fourth Pharyngeal Arch arteries, altered expression of Fgf10 in the Pharyngeal mesenchyme, and abnormal apoptosis in Pharyngeal and cardiac neural crest. The Fgf8 mutants described herein display the complete array of cardiovascular, glandular and craniofacial phenotypes seen in human deletion 22q11 syndromes. This represents the first single gene disruption outside the typically deleted region of human chromosome 22 to fully recapitulate the deletion 22q11 phenotype. FGF8 may operate directly in molecular pathways affected by deletions in 22q11 or function in parallel pathways required for normal development of Pharyngeal Arch and neural crest-derived tissues. In either case, Fgf8 may function as a modifier of the 22q11 deletion and contribute to the phenotypic variability of this syndrome.
-
DEVELOPMENT AND DISEASE An Fgf8 mouse mutant phenocopies human 22q11 deletion syndrome
2002Co-Authors: Deborah U Frank, Judson A Brewer, Louis J Muglia, Mario R Capecchi, Lori K. Fotheringham, Martin Tristani-firouzi, Anne M MoonAbstract:microdeletion detected in humans, is associated with a lifethreatening array of birth defects. Although 90 % of affected individuals share the same three megabase deletion, their phenotype is highly variable and includes craniofacial and cardiovascular anomalies, hypoplasia or aplasia of the thymus with associated deficiency of T cells, hypocalcemia with hypoplasia or aplasia of the parathyroids, and a variety of central nervous system abnormalities. Because ablation of neural crest in chicks produces many features of the deletion 22q11 syndrome, it has been proposed that haploinsufficiency in this region impacts neural crest function during cardiac and Pharyngeal Arch development. Few factors required for migration, survival, proliferation and subsequent differentiation of Pharyngeal Arch neural crest an
Robert E. Poelmann - One of the best experts on this subject based on the ideXlab platform.
-
spatiotemporally separated cardiac neural crest subpopulations that target the outflow tract septum and Pharyngeal Arch arteries
Anatomical Record-advances in Integrative Anatomy and Evolutionary Biology, 2003Co-Authors: Marit J Boot, Adriana Gittenbergerde C Groot, Liesbeth Van Iperen, Beerend P Hierck, Robert E. PoelmannAbstract:We used lacZ-retrovirus labeling combined with neural crest ablation in chick embryos to determine whether the cardiac neural crest cells constitute one group of multipotent cells, or they emigrate from the neural tube in time-dependent groups with different fates in the developing cardiovascular system. We demonstrated that early-migrating cardiac neural crest cells (HH9-10) massively target the aorticopulmonary septum and Pharyngeal Arch arteries, while the late-migrating cardiac neural crest cells (HH12) are restricted to the proximal part of the Pharyngeal Arch arteries. These results suggest a prominent role for early-migrating cells in outflow tract septation, and a function for late-migrating cells in Pharyngeal Arch artery remodeling. We demonstrated in cultures of neural tube explants an intrinsic difference between the early and late populations. However, by performing heterochronic transplantations we showed that the late-migrating cardiac neural crest cells were not developmentally restricted, and could contribute to the condensed mesenchyme of the aorticopulmonary septum when transplanted to a younger environment. Our findings on the exact timing and migratory behavior of cardiac neural crest cells will help narrow the range of factors and genes that are involved in neural crest-related congenital heart diseases.
-
Altered apoptosis pattern during Pharyngeal Arch artery remodelling is associated with aortic Arch malformations in Tgfβ2 knock-out mice
Cardiovascular Research, 2002Co-Authors: Daniel G. M. Molin, Robert E. Poelmann, Lambertus J. Wisse, Thomas C Doetschman, Mohamad Azhar, Marco C. Deruiter, Adriana C. Gittenberger-de GrootAbstract:Objective: The morphogenetic process underlying the remodelling of the embryonic mammalian Pharyngeal Arch artery system is unknown. Within this process, the right sixth, carotid ducts and the distal part of the dorsal aorta (right α-segment) regress. In order to unravel the underlying mechanism we studied the role of apoptosis in the normal regression of Pharyngeal Arch artery segments and in a mouse model that develops aortic Arch malformations. Methods: Normal remodelling was studied in wild-type Swiss (CPBS) and altered remodelling in the Tgfβ2 −/− compared to the Tgfβ2 +/+ (Swiss/Bl6) strain using immunohistochemistry and morphometric analysis. Results: During normal remodelling, apoptosis occurs in the mesenchyme surrounding Pharyngeal Arch arteries before regression starts. With the onset of regression, apoptosis spreads from the mesenchyme to the media. Morphometric evaluation confirms the increase in apoptosis in the actin-positive media of the disappearing segments. In Tgfβ2 −/−, aberrant apoptosis was found in both fourth Arch arteries, whereas the right dorsal aorta lacks apoptosis associated with normal regression. Fourth Arch hypoplasia is the main Arch abnormality. In the most severe case, the fourth Arch is interrupted and the right dorsal aorta α-segment persists, giving rise to aortic Arch interruption type-B and an aberrant right subclavian artery. Conclusions: We have shown for the first time that specific vascular apoptosis patterns accompany normal regression and that the incidence of apoptosis is selectively altered in the case of Arch artery abnormalities in Tgfβ2 knock-out mice.
-
contribution of the cervical sympathetic ganglia to the innervation of the Pharyngeal Arch arteries and the heart in the chick embryo
Anatomical Record-advances in Integrative Anatomy and Evolutionary Biology, 1999Co-Authors: Marlies E Verberne, Adriana Gittenbergerde C Groot, Liesbeth Van Iperen, Robert E. PoelmannAbstract:In the chick heart, sympathetic innervation is derived from the sympathetic neural crest (trunk neural crest arising from somite level 10–20). Since the trunk neural crest gives rise to sympathetic ganglia of their corresponding level, it suggests that the sympathetic neural crest develops into cervical ganglia 4–14. We therefore tested the hypothesis that, in addition to the first thoracic ganglia, the cervical ganglia might contribute to cardiac innervation as well. Putative sympathetic nerve connections between the cervical ganglia and the heart were demonstrated using the differentiation markers tyrosine hydroxylase and HNK-1. In addition, heterospecific transplantation (quail to chick) of the cardiac and trunk neural crest was used to study the relation between the sympathetic neural crest and the cervical ganglia. Quail cells were visualized using the quail nuclear antibody QCPN. The results by immunohistochemical study show that the superior and the middle cervical ganglia and possibly the carotid paraganglia contribute to the carotid nerve. This nerve subsequently joins the nodose ganglion of the vagal nerve via which it contributes to nerve fibers in cardiac vagal branches entering the arterial and venous pole of the heart. In addition, the carotid nerve contributes to nerve fibers connected to putative baro- and chemoreceptors in and near the wall of Pharyngeal Arch arteries suggesting a role of the superior and middle cervical ganglia and the paraganglia of the carotid plexus in sensory afferent innervation. The lower cervical ganglia 13 and 14 contribute predominantly to nerve branches entering the venous pole via the anterior cardinal veins. We did not observe a thoracic contribution. Heterospecific transplantation shows that the cervical ganglia 4–14 as well as the carotid paraganglia are derived from the sympathetic neural crest. The cardiac neural crest does not contribute to the neurons of the cervical ganglia. We conclude that the cervical ganglia contribute to cardiac innervation which explains the contribution of the sympathetic neural crest to the innervation of the chick heart. Anat Rec 255:407–419, 1999. © 1999 Wiley-Liss, Inc.
-
Unilateral Vitelline Vein Ligation Alters Intracardiac Blood Flow Patterns and Morphogenesis in the Chick Embryo
Circulation Research, 1997Co-Authors: B. Hogers, Marco C. Deruiter, A.c. Gittenberger-de Groot, Robert E. PoelmannAbstract:Abstract To study the role of blood flow in normal and abnormal heart development, an embryonic chicken model was developed. The effect of altered venous inflow on normal intracardiac blood flow patterns was studied by visualization of blood flow with India ink. At stage 17, India ink was injected into a capillary or small venule within a specific yolk sac region. After determination of the normal intracardiac flow pattern, the right lateral vitelline vein was ligated, and the new intracardiac flow pattern was studied. Ligation resulted in disturbance of normal intracardiac flow patterns, which was most obvious in the conotruncus. The long-term effect of these abnormal intracardiac flow patterns on the development of the heart and Pharyngeal Arch arteries was investigated by permanent ligation in ovo with a microclip at stage 17 and subsequent evaluation at stages 34, 37, and 45. These experiments revealed anomalies of the vascular system in 58 of the 91 ligated embryos studied. We observed intracardiac malformations consisting of subaortic ventricular septal defects (n=52), semilunar valve anomalies (n=19), atrioventricular anomalies (n=7), and Pharyngeal Arch artery malformations (n=32). It is concluded that abnormal intracardiac blood flow, resulting from hampered venous inflow, may result in serious intracardiac and Pharyngeal Arch artery malformations comparable to defects observed in embryonic chicken models subjected to neural crest ablation, cervical flexure experiments, and excessive retinoic acid treatment.
-
development of the Pharyngeal Arch system related to the pulmonary and bronchial vessels in the avian embryo with a concept on systemic pulmonary collateral artery formation
Circulation, 1993Co-Authors: Marco C. Deruiter, A Gittenbergerde C Groot, L Vaniperen, Robert E. Poelmann, M. M. T. MentinkAbstract:BACKGROUNDThe literature is ambiguous as to the question of the developmental background of systemic-pulmonary collateral arteries. These are found in combination with various congenital heart malformations such as pulmonary atresia. From a clinical point of view, it is of interest to know whether we are dealing with the persistence of transient embryological vessels such as ventral segmental arteries or parts of Pharyngeal Arch arteries or with the prenatal or postnatal recruitment of the bronchial vasculature that normally supplies the lung. This study of the embryology of the extrapulmonary and intrapulmonary vasculature aims at a better understanding of the variations in origin, course, branching pattern, and histology of collateral arteries.METHODS AND RESULTSSerial sections of quail embryos ranging between stage HH11 and stage HH28 were incubated with a monoclonal antibody (alpha MB1) against endothelial cells and their precursors. Additional series of chick embryos were injected with india ink to s...
Kai Jiao - One of the best experts on this subject based on the ideXlab platform.
-
dicer activity in neural crest cells is essential for craniofacial organogenesis and Pharyngeal Arch artery morphogenesis
Mechanisms of Development, 2011Co-Authors: Xuguang Nie, Qin Wang, Kai JiaoAbstract:MicroRNAs (miRNAs) play important roles in regulating gene expression during numerous biological/pathological processes. Dicer encodes an RNase III endonuclease that is essential for generating most, if not all, functional miRNAs. In this work, we applied a conditional gene inactivation approach to examine the function of Dicer during neural crest cell (NCC) development. Mice with NCC-specific inactivation of Dicer died perinatally. Cranial and cardiac NCC migration into target tissues was not affected by Dicer disruption, but their subsequent development was disturbed. NCC derivatives and their associated mesoderm-derived cells displayed massive apoptosis, leading to severe abnormalities during craniofacial morphogenesis and organogenesis. In addition, the 4th Pharyngeal Arch artery (PAA) remodeling was affected, resulting in interrupted aortic Arch artery type B (IAA-B) in mutant animals. Taken together, our results show that Dicer activity in NCCs is essential for craniofacial development and Pharyngeal Arch artery morphogenesis.
-
inactivation of bmp4 from the tbx1 expression domain causes abnormal Pharyngeal Arch artery and cardiac outflow tract remodeling
Cells Tissues Organs, 2011Co-Authors: Xuguang Nie, Christopher B Brown, Qin Wang, Kai JiaoAbstract:Maldevelopment of outflow tract and aortic Arch arteries is among the most common forms of human congenital heart diseases. Both Bmp4 and Tbx1 are known to play critical roles during cardiovascular development. Expression of these two genes partially overlaps in Pharyngeal Arch areas in mouse embryos. In this study, we applied a conditional gene inactivation approach to test the hypothesis that Bmp4 expressed from the Tbx1 expression domain plays a critical role for normal development of outflow tract and Pharyngeal Arch arteries. We showed that inactivation of Bmp4 from Tbx1-expressing cells leads to the spectrum of deformities resembling the cardiovascular defects observed in human DiGeorge syndrome patients. Inactivation of Bmp4 from the Tbx1 expression domain did not cause patterning defects, but affected remodeling of outflow tract and Pharyngeal Arch arteries. Our further examination revealed that Bmp4 is required for normal recruitment/differentiation of smooth muscle cells surrounding the PAA4 and survival of outflow tract cushion mesenchymal cells.