Craniosynostosis and Related Limb Anomalies

Wilkie, A; Oldridge, Michael; Tang, Zequn; Re, Maxson

doi:10.1002/0470846658.ch9

Cited by 32 publications

(9 citation statements)

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“…This positive feedback loop is a likely cause for the premature closing of the sutures, leading to craniosynostosis that is one of the major clinical features of SCS. Studies also showed that Twist1 activity may have a similar effect on FGF signaling in the limb bud [15,55,[63][64][65]. In its regulation of the growth and differentiation of limb bud tissues, Twist1 appears to be also involved in the sonic hedgehog (SHH) pathways, in addition to the FGF signaling pathways.…”

Section: The Function Of Twist1 In Development and Signaling Pathwaysmentioning

confidence: 99%

Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms

et al. 2011

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This article reviews the molecular structure, expression pattern, physiological function, pathological roles and molecular mechanisms of Twist1 in development, genetic disease and cancer. Twist1 is a basic helix-loop-helix domaincontaining transcription factor. It forms homo-or hetero-dimers in order to bind the Nde1 E-box element and activate or repress its target genes. During development, Twist1 is essential for mesoderm specification and differentiation. Heterozygous loss-of-function mutations of the human Twist1 gene cause several diseases including the SaethreChotzen syndrome. The Twist1-null mouse embryos die with unclosed cranial neural tubes and defective head mesenchyme, somites and limb buds. Twist1 is expressed in breast, liver, prostate, gastric and other types of cancers, and its expression is usually associated with invasive and metastatic cancer phenotypes. In cancer cells, Twist1 is upregulated by multiple factors including SRC-1, STAT3, MSX2, HIF-1α, integrin-linked kinase and NF-κB. Twist1 significantly enhances epithelial-mesenchymal transition (EMT) and cancer cell migration and invasion, hence promoting cancer metastasis. Twist1 promotes EMT in part by directly repressing E-cadherin expression by recruiting the nucleosome remodeling and deacetylase complex for gene repression and by upregulating Bmi1, AKT2, YB-1, etc. Emerging evidence also suggests that Twist1 plays a role in expansion and chemotherapeutic resistance of cancer stem cells. Further understanding of the mechanisms by which Twist1 promotes metastasis and identification of Twist1 functional modulators may hold promise for developing new strategies to inhibit EMT and cancer metastasis.

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Section: The Function Of Twist1 In Development and Signaling Pathwaysmentioning

confidence: 99%

Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms

et al. 2011

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“…In the male LDLR−/− model, high fat diets (HFD) upregulate aortic expression of Msx1 and Msx2 67 , two osteogenic transcription factors important in mineralization of the craniofacial skeleton 81, 82 . Bone morphogenetic protein 2 ( BMP2 ) and osteopontin ( OPN ) are also upregulated by diet-induced disease 67 , reflecting contributions first identified in human calcified vessels 83 and valves 84 .…”

Section: Preclinical Models Of Arterial Calcification In the Setmentioning

confidence: 99%

Arterial Calcification in Diabetes Mellitus

Stabley

Towler

2017

ATVB

120

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Diabetes increasingly afflicts our aging and dysmetabolic population. Type 2 diabetes (T2D) and the antecedent metabolic syndrome (MetS) represent the vast majority of the disease burden –increasingly prevalent in children as well as older adults. However, type 1 diabetes (T1D) is also advancing in preadolescent children. As such, a crushing wave of cardiometabolic disease burden now faces our society. Arteriosclerotic calcification is increased in MetS, T2D, and T1D – impairing conduit vessel compliance and function, thereby increasing the risk for dementia, stroke, heart attack, limb ischemia, renal insufficiency and lower extremity amputation. Preclinical models of these dysmetabolic settings have provided insights into the pathobiology of arterial calcification. Osteochondrogenic morphogens in the BMP-Wnt signaling relay and transcriptional regulatory programs driven by Msx and Runx gene families are entrained to innate immune responses – responses activated by the dysmetabolic state – to direct arterial matrix deposition and mineralization. Recent studies implicate the endothelial-mesenchymal transition (EndMT) in contributing to the phenotypic drift of mineralizing vascular progenitors. In this brief overview, we discuss preclinical disease models that provide mechanistic insights – and point to the emerging potential for translating these insights into new therapeutic strategies for our patients challenged with diabetes and its arteriosclerotic complications.

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“…Mutations in the same FGFR genes (either FGFR1, FGFR2, or FGFR3) can result in different craniosynostosis syndromes, thus implicating a common pathologic mechanism with FGFRs proteins gain of function in Pfeiffer, Apert, Muenke, Crouzon, and Jackson-Weiss syndromes [17]. The fact that phenotypes are different in spite of common gene defects might be explained by different interactions with the extracellular matrix constituents [1].…”

Section: Discussionmentioning

confidence: 99%

Q289P mutation in the FGFR2 gene: first report in a patient with type 1 Pfeiffer syndrome

et al. 2008

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When normal development and growth of the calvarial sutures is disrupted, craniosynostosis (premature calvarial suture fusion) may result. Classical craniosynostosis syndromes are autosomal dominant traits and include Apert, Pfeiffer, Crouzon, Jackson-Weiss, and Saethre-Chotzen syndromes. In these conditions, there is premature fusion of skull bones leading to an abnormal head shape, ocular hypertelorism with proptosis, and midface hypoplasia. It is known that mutations in the fibroblast growth factor receptors 1, 2, and 3 cause craniosynostosis. We report on a child with a clinically diagnosed Pfeiffer syndrome that shows the missense point mutation Q289P in exon 8 of the FGFR2 gene. This is a mutation not previously described in the Pfeiffer syndrome but reported in the Crouzon, Jackson-Weiss, and Saethre-Chotzen syndromes. In this paper, we propose the concept that these disorders may represent one genetic condition with phenotypic variability.

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Craniosynostosis and Related Limb Anomalies

Cited by 32 publications

References 0 publications

Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms

Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms

Arterial Calcification in Diabetes Mellitus

Q289P mutation in the FGFR2 gene: first report in a patient with type 1 Pfeiffer syndrome

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