The association study of nonsyndromic cleft lip with or without cleft palate identified risk variants of the $$\varvec{GLI3}$$ G L I 3 gene in a Chinese population

Wang, Yirui; Sun, Yimin; Huang, Yongqing; Pan, Yongchu; Shi, Bing; Ma, Jian; Ma, Lan; Lan, Feifei; Zhou, Yue; Shi, Jiayu; Zhu, Jing; Jiang, Hongbing; Zhang, Lei; Xiao, Xue; Jiang, Min; Yin, Aihua; Yu, Li‐Li; Wang, Lin; Cheng, Jing; Yang, Yinxue

doi:10.1007/s12041-017-0808-5

Cited by 4 publications

(4 citation statements)

References 20 publications

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“…Gli3 acts as an activator of hedgehog pathway targets in the presence of Shh signaling and becomes a repressor when Shh signaling is absent (Wang et al, 2000). Moreover, GLI3 has been associated with NSCLP in human patients (Wang et al, 2017b), and Gli3-null mouse embryos exhibit cleft palate and tongue abnormalities due to improper tongue morphogenesis and failure of palatal shelf elevation and fusion (Table 2, Fig. 3) (Huang et al, 2008).…”

Section: Wnt Signaling Crosstalk With Other Morphogenetic Signaling Pmentioning

confidence: 99%

Wnt signaling in orofacial clefts: crosstalk, pathogenesis and models

Reynolds

Kumari

Rincon

et al. 2019

Disease Models &Amp; Mechanisms

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Diverse signaling cues and attendant proteins work together during organogenesis, including craniofacial development. Lip and palate formation starts as early as the fourth week of gestation in humans or embryonic day 9.5 in mice. Disruptions in these early events may cause serious consequences, such as orofacial clefts, mainly cleft lip and/or cleft palate. Morphogenetic Wnt signaling, along with other signaling pathways and transcription regulation mechanisms, plays crucial roles during embryonic development, yet the signaling mechanisms and interactions in lip and palate formation and fusion remain poorly understood. Various Wnt signaling and related genes have been associated with orofacial clefts. This Review discusses the role of Wnt signaling and its crosstalk with cell adhesion molecules, transcription factors, epigenetic regulators and other morphogenetic signaling pathways, including the Bmp, Fgf, Tgfβ, Shh and retinoic acid pathways, in orofacial clefts in humans and animal models, which may provide a better understanding of these disorders and could be applied towards prevention and treatments.

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Section: Wnt Signaling Crosstalk With Other Morphogenetic Signaling Pmentioning

confidence: 99%

Wnt signaling in orofacial clefts: crosstalk, pathogenesis and models

Reynolds

Kumari

Rincon

et al. 2019

Disease Models &Amp; Mechanisms

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“…Shh signaling also fine-tunes limb patterning ( Johnson et al, 1994 ) and craniofacial development ( Xavier et al, 2016 ) during early fetal life. Therefore, the abnormal regulation of Shh signaling secondary to genetic mutations in the mouse and human results in various congenital malformations, such as neural tube defects (NTDs) ( Wu et al, 2013 ; Lu et al, 2014 ; Kim et al, 2019 ; Renard et al, 2019 ), abnormal brain development ( Dhekne et al, 2018 ; Nagai-Tanima et al, 2020 ), craniofacial abnormalities ( Xavier et al, 2016 ; De Mori et al, 2017 ; Wang et al, 2017 ), and limbs defects ( Anderson et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Wnt1 Lineage Specific Deletion of Gpr161 Results in Embryonic Midbrain Malformation and Failure of Craniofacial Skeletal Development

et al. 2021

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Sonic hedgehog (Shh) signaling regulates multiple morphogenetic processes during embryonic neurogenesis and craniofacial skeletal development. Gpr161 is a known negative regulator of Shh signaling. Nullizygous Gpr161 mice are embryonic lethal, presenting with structural defects involving the neural tube and the craniofacies. However, the lineage specific role of Gpr161 in later embryonic development has not been thoroughly investigated. We studied the Wnt1-Cre lineage specific role of Gpr161 during mouse embryonic development. We observed three major gross morphological phenotypes in Gpr161 cKO (Gpr161 f/f; Wnt1-Cre) fetuses; protrusive tectum defect, encephalocele, and craniofacial skeletal defect. The overall midbrain tissues were expanded and cell proliferation in ventricular zones of midbrain was increased in Gpr161 cKO fetuses, suggesting that protrusive tectal defects in Gpr161 cKO are secondary to the increased proliferation of midbrain neural progenitor cells. Shh signaling activity as well as upstream Wnt signaling activity were increased in midbrain tissues of Gpr161 cKO fetuses. RNA sequencing further suggested that genes in the Shh, Wnt, Fgf and Notch signaling pathways were differentially regulated in the midbrain of Gpr161 cKO fetuses. Finally, we determined that cranial neural crest derived craniofacial bone formation was significantly inhibited in Gpr161 cKO fetuses, which partly explains the development of encephalocele. Our results suggest that Gpr161 plays a distinct role in midbrain development and in the formation of the craniofacial skeleton during mouse embryogenesis.

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“…Previous studies on the association between icTeV and genetic factors have identified several causative gene families and genes, including Hox (10,11), caspase (2,11), paired like homeodomain 1 (7)(8)(9)12), T-box transcription factors and Gli family zinc finger 3 (10,13) genes. However, a major candidate gene remains to be identified (5).…”

Section: Introductionmentioning

confidence: 99%

Whole‑exome sequencing study identifies two novel rare variations associated with congenital talipes equinovarus

Zhang

et al. 2020

Mol Med Report

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congenital talipes equinovarus (cTeV) is a common birth defect with an unclear genetic pathogenesis that results from both genetic and environmental factors. The present study aimed to identify novel variants in patients with cTeV using whole-exome sequencing (WeS) and to investigate the genetic factors responsible for the development of cTeV.a cohort of nine neonates/infants with suspected cTeV was recruited. Subsequently, sequential tests, including chromosome karyotyping and WeS, were performed for each of the participants. Familial validation was performed using Sanger sequencing and low-coverage copy-number variation (cnV) sequencing. a novel cnV containing the mediator complex subunit 13l gene at 12q24.21-q24.23 was detected by WeS and further investigated by cnVseq. additionally, a novel de novo missense variation, transforming growth factor-β receptor 2: c.1280T>C, was identified by WES and further investigated by Sanger sequencing. The two identified variations were hypothesized to be causative genetic factors for the development of cTeV in the two cases the variations were identified in. In the present study, two pathogenic variations (one cnV and one single-base variation) were detected in two chinese families with cTeV. The results of the present study may aid in investigating the molecular basis of cTeV; however, further investigation is required.

show abstract

The association study of nonsyndromic cleft lip with or without cleft palate identified risk variants of the $$\varvec{GLI3}$$ G L I 3 gene in a Chinese population

Cited by 4 publications

References 20 publications

Wnt signaling in orofacial clefts: crosstalk, pathogenesis and models

Wnt signaling in orofacial clefts: crosstalk, pathogenesis and models

Wnt1 Lineage Specific Deletion of Gpr161 Results in Embryonic Midbrain Malformation and Failure of Craniofacial Skeletal Development

Whole‑exome sequencing study identifies two novel rare variations associated with congenital talipes equinovarus

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