Dataset Information

Pax9 and Gbx2 Interact in the Pharyngeal Endoderm to Control Cardiovascular Development.

ABSTRACT: The correct formation of the aortic arch arteries depends on a coordinated and regulated gene expression profile within the tissues of the pharyngeal arches. Perturbation of the gene regulatory networks in these tissues results in congenital heart defects affecting the arch arteries and the outflow tract of the heart. Aberrant development of these structures leads to interruption of the aortic arch and double outlet right ventricle, abnormalities that are a leading cause of morbidity in 22q11 Deletion Syndrome (DS) patients. We have recently shown that Pax9 functionally interacts with the 22q11DS gene Tbx1 in the pharyngeal endoderm for 4th pharyngeal arch artery morphogenesis, with double heterozygous mice dying at birth with interrupted aortic arch. Mice lacking Pax9 die perinatally with complex cardiovascular defects and in this study we sought to validate further potential genetic interacting partners of Pax9, focussing on Gbx2 which is down-regulated in the pharyngeal endoderm of Pax9-null embryos. Here, we describe the Gbx2-null cardiovascular phenotype and demonstrate a genetic interaction between Gbx2 and Pax9 in the pharyngeal endoderm during cardiovascular development.

SUBMITTER: Stothard CA

PROVIDER: S-EPMC7344924 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

<i>Pax9</i> and <i>Gbx2</i> Interact in the Pharyngeal Endoderm to Control Cardiovascular Development.

Stothard Catherine A CA Mazzotta Silvia S Vyas Arjun A Schneider Jurgen E JE Mohun Timothy J TJ Henderson Deborah J DJ Phillips Helen M HM Bamforth Simon D SD

Journal of cardiovascular development and disease 20200525 2

The correct formation of the aortic arch arteries depends on a coordinated and regulated gene expression profile within the tissues of the pharyngeal arches. Perturbation of the gene regulatory networks in these tissues results in congenital heart defects affecting the arch arteries and the outflow tract of the heart. Aberrant development of these structures leads to interruption of the aortic arch and double outlet right ventricle, abnormalities that are a leading cause of morbidity in 22q11 De ...[more]

PMID: 32466118

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Project description:BackgroundSuccessful 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.ResultsIn 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.ConclusionsMsx1 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.

Dataset Information

Pax9 and Gbx2 Interact in the Pharyngeal Endoderm to Control Cardiovascular Development.

Publications

<i>Pax9</i> and <i>Gbx2</i> Interact in the Pharyngeal Endoderm to Control Cardiovascular Development.

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Pax9 and Gbx2 Interact in the Pharyngeal Endoderm to Control Cardiovascular Development.

Publications

&lt;i&gt;Pax9&lt;/i&gt; and &lt;i&gt;Gbx2&lt;/i&gt; Interact in the Pharyngeal Endoderm to Control Cardiovascular Development.

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OmicsDI is part of the ELIXIR infrastructure

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<i>Pax9</i> and <i>Gbx2</i> Interact in the Pharyngeal Endoderm to Control Cardiovascular Development.