Role of Semaphorin Signaling During Cardiovascular Development

Sun, Qianchuang; Liu, Shuyan; Liu, Kexiang; Jiao, Kai

doi:10.1161/jaha.118.008853

Cited by 16 publications

(11 citation statements)

References 83 publications

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“…Signalling between the pharyngeal endoderm and NCC does occur (Graham et al, 2005) so it is therefore possible that signals emanating from the pharyngeal endoderm under Pax9 control are necessary to influence the differentiation of NCCs into SMCs; without these signals, the 3rd PAAs are not supported during the remodelling phase of arch artery development and they collapse. The top two GSEA pathways identified from the RNA-seq data were ‘extracellular matrix organisation’ and ‘axon guidance’, and these could be relevant for a NCC-derived phenotype, particularly as the extracellular matrix is known to be crucial for the migration of NCCs (Henderson and Copp, 1997; Perris and Perissinotto, 2000) and the slit, ephrin, semaphorin and plexin genes listed under ‘axon guidance’ are usually associated with NCC expression or migration in cardiovascular development (Epstein et al, 2015; Kirby and Hutson, 2010; Sun et al, 2018). There is, however, an alternative explanation for the collapse of the 3rd PAAs.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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Developmental defects affecting the heart and aortic arch arteries are a significant phenotype observed in individuals with 22q11 deletion syndrome and are caused by a microdeletion on chromosome 22q11. TBX1, one of the deleted genes, is expressed throughout the pharyngeal arches and is considered a key gene, when mutated, 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 that affect 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 with Tbx1 heterozygous mice. Using a novel Pax9Cre allele, we demonstrated that the site of this Tbx1-Pax9 genetic interaction is the pharyngeal endoderm, therefore revealing that a Tbx1-Pax9-controlled signalling mechanism emanating from the pharyngeal endoderm is required for crucial tissue interactions during normal morphogenesis of the pharyngeal arch artery system.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…Semaphorins have previously been shown to play critical functions in cardiogenesis and blood vessel development ( 89 ), however more recently they have been explored as biomarkers for various inflammatory cardiovascular conditions in critically ill patients. In a study of patients with clinical suspicion of infectious endocarditis (IE) the investigators performed proteomic analysis of serum to identify putative biomarkers of IE by means of gel electrophoresis and mass spectrometry.…”

Section: Acute Cardiac Dysfunctionmentioning

confidence: 99%

The Role of Semaphorins and Their Receptors in Innate Immune Responses and Clinical Diseases of Acute Inflammation

2021

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Semaphorins are a group of proteins that have been studied extensively for their critical function in neuronal development. They have been shown to regulate airway development, tumorigenesis, autoimmune diseases, and the adaptive immune response. Notably, emerging literature describes the role of immunoregulatory semaphorins and their receptors, plexins and neuropilins, as modulators of innate immunity and diseases defined by acute injury to the kidneys, abdomen, heart and lungs. In this review we discuss the pathogenic functions of semaphorins in clinical conditions of acute inflammation, including sepsis and acute lung injury, with a focus on regulation of the innate immune response as well as potential future therapeutic targeting.

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“…17 SEMAs are extracellular signalling proteins that include both secreted (classes 2 and 3) and membrane-tethered (classes 1, 4-7 and V) forms. 18 However, some members of the membrane-tethered SEMA family, such as Semaphorin 4A (SEMA4A), Semaphorin 4D and Semaphorin 5A, can become soluble after proteolytic cleavage. 19 Classes 1 and 2 are found in invertebrates, classes 3 to 7 are present in vertebrates, and class V SEMAs are found only in viruses.…”

Section: Studies Investigatingmentioning

confidence: 99%

Insights into the regulatory role of Plexin D1 signalling in cardiovascular development and diseases

Zhang

Jia

et al. 2021

J Cellular Molecular Medi

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Plexins (PLXNs) were discovered by Takagi and colleagues in 1987 in the Xenopus laevis tadpole model 1 while the researchers were screening molecules in the optic tectum using monoclonal antibodies (MAbs). The plexin protein is an antigen of a MAb, that is, MAb-B2, and constituted a new type one membrane glycoprotein. 2 The new protein was subsequently renamed plexin because it preferentially binds the retinal plexiform layer. 3,4 The first human PLXNs were identified by Maestrini and colleagues in 1996, 5 and in 1999, Tamagnone and colleagues identified 4 classes of PLXNs in vertebrates (A to D) based on the sequence similarities of their ectodomains. 6 Subsequently, studies by several research groups unravelled the structure of PLXNs (Figure 1). 7 PLXNs contain an extracellular sema domain, one membrane-spanning region and a cytoplasmic domain that has a GTPase-activating protein (GAP) domain and a Rho GTPase binding domain (RBD) insert. 7,8 Although this domain is

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Role of Semaphorin Signaling During Cardiovascular Development

Cited by 16 publications

References 83 publications

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

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

The Role of Semaphorins and Their Receptors in Innate Immune Responses and Clinical Diseases of Acute Inflammation

Insights into the regulatory role of Plexin D1 signalling in cardiovascular development and diseases

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