scholarly journals Pharyngeal arch artery defects and lethal malformations of the aortic arch and its branches in mice deficient for the Hrt1/Hey1 transcription factor

2016 ◽  
Vol 139 ◽  
pp. 65-73 ◽  
Author(s):  
Masahide Fujita ◽  
Masahide Sakabe ◽  
Tomoko Ioka ◽  
Yusuke Watanabe ◽  
Yumi Kinugasa-Katayama ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Aortic Arch ◽  
Pharyngeal Arch ◽  
Pharyngeal Arch Artery

scholarly journals Altered apoptosis pattern during pharyngeal arch artery remodelling is associated with aortic arch malformations in Tgfβ2 knock-out mice

2002 ◽  
Vol 56 (2) ◽  
pp. 312-322 ◽  
Author(s):  
D MOLIN ◽  
M DERUITER ◽  
L WISSE ◽  
M AZHAR ◽  
T DOETSCHMAN ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Pharyngeal Arch ◽  
Knock Out ◽  
Pharyngeal Arch Artery ◽  
Knock Out Mice

scholarly journals Pax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4th pharyngeal arch artery morphogenesis

2019 ◽  
Author(s):  
Helen M. Phillips ◽  
Catherine A. Stothard ◽  
Wasay Mohiuddin Shaikh Qureshi ◽  
Anastasia I. Kousa ◽  
J. Alberto Briones-Leon ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Genetic Interaction ◽  
Interrupted Aortic Arch ◽  
Outflow Tract ◽  
Pharyngeal Arch ◽  
Cardiovascular Development ◽  
Developmental Defects ◽  
Pharyngeal Endoderm ◽  
Pharyngeal Arch Artery ◽  
Aortic Arch Arteries

AbstractDevelopmental defects affecting the heart and aortic arch arteries are a key phenotype observed in DiGeorge syndrome patients and are caused by a microdeletion on chromosome 22q11. Heterozygosity of TBX1, one of the deleted genes, is expressed throughout the pharyngeal arches and is considered a key component for the arch artery defects. Pax9 is expressed in the pharyngeal endoderm and is downregulated in Tbx1 mutant mice. We show here that Pax9 deficient mice are born with complex cardiovascular malformations affecting the outflow tract and aortic arch arteries with failure of the 3rd and 4th pharyngeal arch arteries to form correctly. Transcriptome analysis indicated that Pax9 and Tbx1 may function together, and mice double heterozygous for Tbx1/Pax9 presented with a significantly increased incidence of interrupted aortic arch when compared to Tbx1 heterozygous mice. Using a novel Pax9Cre allele we demonstrated that the site of this Tbx1-Pax9 genetic interaction is in the pharyngeal endoderm, therefore revealing that a Tbx1/Pax9-controlled signalling mechanism emanating from the pharyngeal endoderm is required for critical tissue interactions during normal morphogenesis of the pharyngeal arch artery system.Summary statementPax9 is required for outflow tract and aortic arch development, and functions together with Tbx1 in the pharyngeal endoderm for 4th arch artery formation.

scholarly journals TGF-β Signaling Is Necessary and Sufficient for Pharyngeal Arch Artery Angioblast Formation

Cell Reports ◽  
2017 ◽  
Vol 20 (4) ◽  
pp. 973-983 ◽  
Author(s):  
Maryline Abrial ◽  
Noëlle Paffett-Lugassy ◽  
Spencer Jeffrey ◽  
Daniel Jordan ◽  
Evan O’Loughlin ◽  
...  
Keyword(s):  
Pharyngeal Arch ◽  
Pharyngeal Arch Artery ◽  
Necessary And Sufficient

A genetic link between Tbx1 and fibroblast growth factor signaling

Development ◽  
2002 ◽  
Vol 129 (19) ◽  
pp. 4605-4611 ◽  
Author(s):  
Francesca Vitelli ◽  
Ilaria Taddei ◽  
Masae Morishima ◽  
Erik N. Meyers ◽  
Elizabeth A. Lindsay ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Expression Patterns ◽  
Pharyngeal Arch ◽  
Growth Factor Signaling ◽  
Expression Domain ◽  
Primary Defect ◽  
Genetic Link ◽  
Pharyngeal Endoderm ◽  
Pharyngeal Arch Arteries ◽  
Tbx1 Haploinsufficiency

Tbx1 haploinsufficiency causes aortic arch abnormalities in mice because of early growth and remodeling defects of the fourth pharyngeal arch arteries. The function of Tbx1 in the development of these arteries is probably cell non-autonomous, as the gene is not expressed in structural components of the artery but in the surrounding pharyngeal endoderm. We hypothesized that Tbx1 may trigger signals from the pharyngeal endoderm directed to the underlying mesenchyme. We show that the expression patterns of Fgf8 and Fgf10, which partially overlap with Tbx1 expression pattern, are altered in Tbx1–/– mutants. In particular, Fgf8 expression is abolished in the pharyngeal endoderm. To understand the significance of this finding for the pathogenesis of the mutant Tbx1 phenotype, we crossed Tbx1 and Fgf8 mutants. Double heterozygous Tbx1+/–;Fgf8+/– mutants present with a significantly higher penetrance of aortic arch artery defects than do Tbx1+/–;Fgf8+/+ mutants, while Tbx1+/+;Fgf8+/– animals are normal. We found that Fgf8 mutation increases the severity of the primary defect caused by Tbx1 haploinsufficiency, i.e. early hypoplasia of the fourth pharyngeal arch arteries, consistent with the time and location of the shared expression domain of the two genes. Hence, Tbx1 and Fgf8 interact genetically in the development of the aortic arch. Our data provide the first evidence of a genetic link between Tbx1 and FGF signaling, and the first example of a modifier of the Tbx1 haploinsufficiency phenotype. We speculate that the FGF8 locus might affect the penetrance of cardiovascular defects in individuals with chromosome 22q11 deletions involving TBX1.

scholarly journals Foxc2 in pharyngeal arch mesenchyme is important for aortic arch artery remodelling and ventricular septum formation

2015 ◽  
Vol 36 (4) ◽  
pp. 235-245 ◽  
Author(s):  
Mohammad Khaja Mafij UDDIN ◽  
Wataru KIMURA ◽  
Tomoyuki ISHIKURA ◽  
Haruhiko KOSEKI ◽  
Nobuaki YOSHIDA ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Ventricular Septum ◽  
Pharyngeal Arch

scholarly journals Cell - ECM Interactions Play Multiple Essential Roles in Aortic Arch Development

2020 ◽  
Author(s):  
Michael Warkala ◽  
Dongying Chen ◽  
AnnJosette Ramirez ◽  
Ali Jubran ◽  
Michael J Schonning ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Developmental Stages ◽  
Lineage Tracing ◽  
Confocal Imaging ◽  
Pharyngeal Arch ◽  
Cellular Mechanisms ◽  
Integrin Α5β1 ◽  
Pharyngeal Arches ◽  
Heart Field ◽  
Pharyngeal Arch Arteries

Rationale: Defects in the morphogenesis of the 4th pharyngeal arch arteries (PAAs) give rise to lethal birth defects. Understanding genes and mechanisms regulating PAA formation will provide important insights into the etiology and treatments for congenital heart disease. Objective: Cell-ECM interactions play essential roles in the morphogenesis of PAAs and their derivatives, the aortic arch artery (AAA) and its major branches; however, their specific functions are not well-understood. Previously, we demonstrated that integrin α5β1 and fibronectin (Fn1) expressed in the Isl1 lineages regulate PAA formation. The objective of the current studies was to investigate cellular mechanisms by which integrin α5β1 and Fn1 regulate AAA morphogenesis. Methods and Results: Using temporal lineage tracing, whole-mount confocal imaging, and quantitative analysis of the second heart field (SHF) and endothelial cell (EC) dynamics, we show that the majority of PAA EC progenitors arise by E7.5 in the SHF and contribute to pharyngeal arch endothelium between E7.5 and E9.5. Consequently, SHF-derived ECs in the pharyngeal arches form a uniform plexus of small blood vessels, which remodels into the PAAs by 35 somites. The remodeling of the vascular plexus is orchestrated by signals dependent on the pharyngeal ECM microenvironment, extrinsic to the endothelium. Conditional ablation of integrin α5β1 or Fn1 in the Isl1 lineages showed that signaling by the ECM regulates AAA morphogenesis at multiple steps: 1) accumulation of SHF-derived ECs in the pharyngeal arches, 2) remodeling of the uniform EC plexus in the 4th arches into the PAAs; and 3) differentiation of neural crest-derived cells adjacent to the PAA endothelium into vascular smooth muscle cells. Conclusions: PAA formation is a multi-step process entailing dynamic contribution of SHF-derived ECs to pharyngeal arches, the remodeling of endothelial plexus into the PAAs, and the remodeling of the PAAs into the AAA and its major branches. Cell-ECM interactions regulated by integrin α5β1 and Fn1 play essential roles at each of these developmental stages.

scholarly journals Cell – ECM interactions play distinct and essential roles at multiple stages during the development of the aortic arch

2020 ◽  
Author(s):  
Michael Warkala ◽  
Dongying Chen ◽  
Ali Jubran ◽  
AnnJosette Ramirez ◽  
Michael Schonning ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Developmental Stages ◽  
Lineage Tracing ◽  
Confocal Imaging ◽  
Pharyngeal Arch ◽  
Cellular Mechanisms ◽  
Integrin Α5β1 ◽  
Pharyngeal Arches ◽  
Heart Field ◽  
Pharyngeal Arch Arteries

RationaleDefects in the morphogenesis of the 4th pharyngeal arch arteries (PAAs) give rise to lethal birth defects. Understanding genes and mechanisms regulating PAA formation will provide important insights into the etiology and treatments for congenital heart disease.ObjectiveCell-ECM interactions play essential roles in the morphogenesis of PAAs and their derivatives, the aortic arch artery (AAA) and its major branches; however, their specific functions are not well-understood. Previously, we demonstrated that integrin α5β1 and fibronectin (Fn1) expressed in the Isl1 lineages regulate PAA formation. The objective of these studies was to investigate cellular mechanisms by which integrin α5β1 and Fn1 regulate AAA morphogenesis.Methods and ResultsUsing temporal lineage tracing, whole-mount confocal imaging, and quantitative analysis of the second heart field (SHF) and endothelial cell (EC) dynamics, we show that the majority of PAA EC progenitors arise by E7.5 in the SHF and populate pharyngeal arch mesenchyme between E7.5 and E9.5. Consequently, SHF-derived ECs in the pharyngeal arches become organized into a uniform plexus of small blood vessels, which becomes remodeled into the PAAs between 31 – 35 somites. The remodeling of the vascular plexus is orchestrated by signals dependent on pharyngeal ECM microenvironment extrinsic to the endothelium. Conditional ablation of integrin α5β1 or Fn1 in the Isl1 lineages showed that signaling by the ECM regulates AAA morphogenesis at multiple steps: 1) the recruitment of the SHF-derived ECs into the pharyngeal arches, 2) the remodeling of the uniform EC plexus in the 4th arches into the PAAs; and 3) differentiation of neural crest-derived cells abutting the PAA endothelium into vascular smooth muscle cells.ConclusionsPAA formation is a multi-step process entailing dynamic contribution of SHF-derived ECs to pharyngeal arches, the remodeling of endothelial plexus into the PAAs, and the remodeling of the PAAs into the AAA and its major branches. Cell-ECM interactions regulated by integrin α5β1 and Fn1 play essential roles at each of these developmental stages.

How best to describe the pharyngeal arch arteries when the fifth arch does not exist?

2020 ◽  
Vol 30 (11) ◽  
pp. 1708-1710
Author(s):  
Robert H. Anderson ◽  
Simon D. Bamforth ◽  
Saurabh Kumar Gupta
Keyword(s):  
Aortic Arch ◽  
Human Fetus ◽  
Right Aortic Arch ◽  
Developmental Changes ◽  
Pharyngeal Arch ◽  
Pharyngeal Arches ◽  
Pharyngeal Arch Arteries ◽  
Collateral Channel

AbstractIn the accompanying article appearing in this issue of the Journal, Prabhu and his colleagues, from Bengalaru in India, describe their experience with patients having a right aortic arch. They discuss the fact that the anomalous arrangements they encountered can all be interpreted on the basis of the hypothetical double arch proposed by Edwards. They point to the fact that interpretation of the developmental changes underscoring the production of the double arch is currently confused by reference to the so-called Rathke diagram, in which six sets of arteries are shown extending through the mesenchyme of the pharyngeal arches. As the authors point out, Graham and his associates have now shown that the alleged fifth set of pharyngeal arches do not exist. Based on our own observations, we endorse this statement. It means that new explanations must now be provided for the lesions previously described on the basis of persistence of the alleged artery of the fifth pharyngeal arch. We have previously claimed to have observed such an artery in a human fetus. We now believe, on the basis of our latest findings, that our earlier observation is better explained on the basis of presence of a collateral channel. We suggest that the so-called “fifth arch arteries” are themselves then best explained either on the basis of existence of such collateral channels, or remodelling of the aortic sac, which is the manifold, during development, that gives rise to the pharyngeal arch arteries.

Essential roles of the winged helix transcription factor MFH-1 in aortic arch patterning and skeletogenesis

Development ◽  
1997 ◽  
Vol 124 (22) ◽  
pp. 4627-4638 ◽  
Author(s):  
K. Iida ◽  
H. Koseki ◽  
H. Kakinuma ◽  
N. Kato ◽  
Y. Mizutani-Koseki ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neural Crest ◽  
Aortic Arch ◽  
Interrupted Aortic Arch ◽  
Targeted Mutagenesis ◽  
Winged Helix ◽  
Cartilaginous Tissues ◽  
Early Embryos ◽  
Skeletal Defects ◽  
Winged Helix Transcription Factor

Mesenchyme Fork Head-1 (MFH-1) is a forkhead (also called winged helix) transcription factor defined by a common 100-amino acid DNA-binding domain. MFH-1 is expressed in non-notochordal mesoderm in the prospective trunk region and in cephalic neural-crest and cephalic mesoderm-derived mesenchymal cells in the prechordal region of early embryos. Subsequently, strong expression is localized in developing cartilaginous tissues, kidney and dorsal aortas. To investigate the developmental roles of MFH-1 during embryogenesis, mice lacking the MFH-1 locus were generated by targeted mutagenesis. MFH-1-deficient mice died embryonically and perinatally, and exhibited interrupted aortic arch and skeletal defects in the neurocranium and the vertebral column. Interruption of the aortic arch seen in the mutant mice was the same as in human congenital anomalies. These results suggest that MFH-1 has indispensable roles during the extensive remodeling of the aortic arch in neural-crest-derived cells and in skeletogenesis in cells derived from the neural crest and the mesoderm.

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