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

Development ◽  
2019 ◽  
Vol 146 (18) ◽  
pp. dev177618 ◽  
Author(s):  
Helen M. Phillips ◽  
Catherine A. Stothard ◽  
Wasay M. Shaikh Qureshi ◽  
Anastasia I. Kousa ◽  
J. Alberto Briones-Leon ◽  
...  
Keyword(s):  
Pharyngeal Arch ◽  
Cardiovascular Development ◽  
Pharyngeal Endoderm ◽  
Pharyngeal Arch Artery

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.

Fgf8is required for pharyngeal arch and cardiovascular development in the mouse

Development ◽  
2002 ◽  
Vol 129 (19) ◽  
pp. 4613-4625 ◽  
Author(s):  
Radwan Abu-Issa ◽  
Graham Smyth ◽  
Ida Smoak ◽  
Ken-ichi Yamamura ◽  
Erik N. Meyers
Keyword(s):  
Craniofacial Development ◽  
Mouse Embryos ◽  
Pharyngeal Arch ◽  
Compound Heterozygous ◽  
Cardiovascular Development ◽  
Early Analysis ◽  
Pharyngeal Arches ◽  
The Face ◽  
Cardiovascular Defects ◽  
Additional Role

We present here an analysis of cardiovascular and pharyngeal arch development in mouse embryos hypomorphic for Fgf8. Previously, we have described the generation of Fgf8 compound heterozygous (Fgf8neo/–) embryos. Although early analysis demonstrated that some of these embryos have abnormal left-right (LR) axis specification and cardiac looping reversals, the number and type of cardiac defects present at term suggested an additional role for Fgf8 in cardiovascular development. Most Fgf8neo/– mutant embryos survive to term with abnormal cardiovascular patterning, including outflow tract, arch artery and intracardiac defects. In addition, these mutants have hypoplastic pharyngeal arches, small or absent thymus and abnormal craniofacial development. Neural crest cells (NCCs) populate the pharyngeal arches and contribute to many structures of the face, neck and cardiovascular system, suggesting that Fgf8 may be required for NCC development. Fgf8 is expressed within the developing pharyngeal arch ectoderm and endoderm during NCC migration through the arches. Analysis of NCC development in Fgf8neo/– mutant embryos demonstrates that NCCs are specified and migrate, but undergo cell death in areas both adjacent and distal to where Fgf8 is normally expressed. This study defines the cardiovascular defects present in Fgf8 mutants and supports a role for Fgf8 in development of all the pharyngeal arches and in NCC survival.

scholarly journals Clarification of the identity of the mammalian fifth pharyngeal arch artery

2012 ◽  
Vol 26 (2) ◽  
pp. 173-182 ◽  
Author(s):  
Simon D. Bamforth ◽  
Bill Chaudhry ◽  
Michael Bennett ◽  
Robert Wilson ◽  
Timothy J. Mohun ◽  
...  
Keyword(s):  
Pharyngeal Arch ◽  
Pharyngeal Arch Artery

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 Msx1 haploinsufficiency modifies the Pax9-deficient cardiovascular phenotype

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ramada R. Khasawneh ◽  
Ralf Kist ◽  
Rachel Queen ◽  
Rafiqul Hussain ◽  
Jonathan Coxhead ◽  
...  
Keyword(s):  
Neural Crest ◽  
Aortic Arch ◽  
Thyroid Cartilage ◽  
Neural Crest Cell ◽  
Pharyngeal Arch ◽  
Palate Development ◽  
The Third ◽  
Pharyngeal Endoderm ◽  
Cardiovascular Defects ◽  
Crest Cell

Abstract Background Successful embryogenesis relies on the coordinated interaction between genes and tissues. The transcription factors Pax9 and Msx1 genetically interact during mouse craniofacial morphogenesis, and mice deficient for either gene display abnormal tooth and palate development. Pax9 is expressed specifically in the pharyngeal endoderm at mid-embryogenesis, and mice deficient for Pax9 on a C57Bl/6 genetic background also have cardiovascular defects affecting the outflow tract and aortic arch arteries giving double-outlet right ventricle, absent common carotid arteries and interruption of the aortic arch. Results In this study we have investigated both the effect of a different genetic background and Msx1 haploinsufficiency on the presentation of the Pax9-deficient cardiovascular phenotype. Compared to mice on a C57Bl/6 background, congenic CD1-Pax9–/– mice displayed a significantly reduced incidence of outflow tract defects but aortic arch defects were unchanged. Pax9–/– mice with Msx1 haploinsufficiency, however, have a reduced incidence of interrupted aortic arch, but more cases with cervical origins of the right subclavian artery and aortic arch, than seen in Pax9–/– mice. This alteration in arch artery defects was accompanied by a rescue in third pharyngeal arch neural crest cell migration and smooth muscle cell coverage of the third pharyngeal arch arteries. Although this change in phenotype could theoretically be compatible with post-natal survival, using tissue-specific inactivation of Pax9 to maintain correct palate development whilst inducing the cardiovascular defects was unable to prevent postnatal death in the mutant mice. Hyoid bone and thyroid cartilage formation were abnormal in Pax9–/– mice. Conclusions Msx1 haploinsufficiency mitigates the arch artery defects in Pax9–/– mice, potentially by maintaining the survival of the 3rd arch artery through unimpaired migration of neural crest cells to the third pharyngeal arches. With the neural crest cell derived hyoid bone and thyroid cartilage also being defective in Pax9–/– mice, we speculate that the pharyngeal endoderm is a key signalling centre that impacts on neural crest cell behaviour highlighting the ability of cells in different tissues to act synergistically or antagonistically during embryo development.

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