Grhl1 deficiency affects inner ear development in zebrafish

Liu, Fei; Yang, Fan; Wen, Danping; Xia, Wenjun; Hao, Lili; Hu, Jiongjiong; Zong, Jie; Shen, Xiaofang; Ma, Jing; Jiang, Nan; Sun, Song; Zhang, Jin; Wang, Huijun; Wang, Xu; Ma, Zhiyuan; Ma, Duan

doi:10.1387/ijdb.140230fl

Cited by 11 publications

(10 citation statements)

References 32 publications

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“…A variety of human, mouse and fish studies suggest reduced expression of Grhl3, Dlx3, Dlx5 and Osx1 could explain the defects we found in calcium and phosphate metabolism (Dworkin et al, 2014;Han et al, 2011;Isaac et al, 2014;Lapunzina et al, 2010;Liu et al, 2015;Nguyen et al, 2013;Ting et al, 2003a). Mineralization of the endochondral skeleton is a complex biological process involving the formation of a calcium phosphate hydroxyapatite crystal that is deposited into an organic extracellular matrix composed primarily of type I collagen.…”

Section: Discussionmentioning

confidence: 87%

Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2

et al. 2016

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Enhanced BMP or canonical Wnt (cWnt) signaling are therapeutic strategies employed to enhance bone formation and fracture repair, but the mechanisms each pathway utilizes to specify cell fate of bone-forming osteoblasts remain poorly understood. Among all BMPs expressed in bone, we find that singular deficiency of Bmp2 blocks the ability of cWnt signaling to specify osteoblasts from limb bud or bone marrow progenitors. When exposed to cWnts, Bmp2-deficient cells fail to progress through the Runx2/ Osx1 checkpoint and thus do not upregulate multiple genes controlling mineral metabolism in osteoblasts. Cells lacking Bmp2 after induction of Osx1 differentiate normally in response to cWnts, suggesting that pre-Osx1+ osteoprogenitors are an essential source and a target of BMP2. Our analysis furthermore reveals Grainyhead-like 3 (Grhl3) as a transcription factor in the osteoblast gene regulatory network induced during bone development and bone repair, which acts upstream of Osx1 in a BMP2-dependent manner. The Runx2/Osx1 transition therefore receives crucial regulatory inputs from BMP2 that are not compensated for by cWnt signaling, and this is mediated at least in part by induction and activation of Grhl3.

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Section: Discussionmentioning

confidence: 87%

Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2

et al. 2016

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“…The GRHL1 gene is located at the chromosomal position 2p25 in humans. 14 In a mouse model, the loss of GRHL1 significantly GRHL2 GRHL3 Figure 2 The immunohistochemical staining of GRHL genes in carcinoma tissues and adjacent tissues in patients with CC obtained from HPA database.…”

Section: Discussionmentioning

confidence: 99%

<p>Grainyhead-Like Genes Family May Act as Novel Biomarkers in Colon Cancer</p>

Yuan¹,

Wang

Fang

2020

OTT

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Objective: The Grainyhead-like (GRHL) genes family were reported to participate in the development of a number of diseases. This study was designed to investigate the role of GRHL genes family in colon cancer (CC). Methods: In this study, the transcriptional levels of GRHL genes family in patients with CC from GEPIA were explored. Meanwhile, the immunohistochemical data of the GRHL genes family were also obtained in the HPA database. Additionally, we re-identified the mRNA of these genes via real-time PCR. Furthermore, the association between the levels of GRHL genes and stage plot as well as survival condition including overall survival and disease-free survival of patients with CC was analyzed. Finally, by transfecting with specific-siRNA, clone formation assay was performed to observe the role of GRHL genes family in the proliferation of SW480 human colon cancer cells. Results: We found that the mRNA and protein levels of GRHL1, GRHL2 and GRHL3 were significantly higher in CC tissues than in normal colon tissues. Additionally, GRHL1, GRHL2 and GRHL3 were significantly associated with the stages of CC. The Kaplan-Meier plotter showed that the low levels of GRHL1, GRHL2 and GRHL3 conferred a better overall survival of patients with CC while the high levels of GRHL1 and GRHL3 were associated with poor disease-free survival. Knockdown of GRHL1, GRHL2 and GRHL3 siHgnificantly inhibited the ability of colony formation of human colon cancer cells. Conclusion: Our study demonstrated that GRHL genes are involved in the prognosis and survival in patients with CC, the inhibition of which may suppress the proliferation of colon cancer cells.

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“…Together with GRHL1, these two homologous proteins have similar sequences and functions. A grhl1 down-regulated zebrafish model exhibited inner ear developmental malformations, including missing otoliths, disordered and abnormal number of hair cells in the inner ear and lateral line, and sound insensitivity [ 38 ]. Remarkably, the mutant zebrafish swam in circles, being hair cell apoptosis evident.…”

Section: Sensorineural Hearing Loss With Variable Vestibular Dysfunctmentioning

confidence: 99%

“…Using electron microscopy, desmosomes in the otic sensory epithelium were found to be damaged. These defects were partially rescued by treatment with either GRHL1 or its target gene, DSG1 [ 38 ].…”

Section: Sensorineural Hearing Loss With Variable Vestibular Dysfunctmentioning

confidence: 99%

Genetics of vestibular disorders: pathophysiological insights

et al. 2016

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The two most common vestibular disorders are motion sickness and vestibular migraine, affecting 30 and 1–2 % of the population respectively. Both are related to migraine and show a familial trend. Bilateral vestibular hypofunction is a rare condition, and some of patients also present cerebellar ataxia and neuropathy. We present recent advances in the genetics of vestibular disorders with familial aggregation. The clinical heterogeneity observed in different relatives of the same families suggests a variable penetrance and the interaction of several genes in each family. Some Mendelian sensorineural hearing loss also exhibits vestibular dysfunction, including DFNA9, DFNA11, DFNA15 and DFNA28. However, the most relevant finding during the past years is the familial clustering observed in Meniere’s disease. By using whole exome sequencing and combining bioinformatics tools, novel variants in DTNA and FAM136A genes have been identified in familial Meniere’s disease, and this genomic strategy will facilitate the discovery of the genetic basis of familial vestibular disorders.

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Grhl1 deficiency affects inner ear development in zebrafish

Cited by 11 publications

References 32 publications

Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2

Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2

<p>Grainyhead-Like Genes Family May Act as Novel Biomarkers in Colon Cancer</p>

Genetics of vestibular disorders: pathophysiological insights

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