Grhl3 modulates epithelial structure formation of the circumvallate papilla during mouse development

Adhikari, Nirpesh; Neupane, Sanjiv; Gwon, Gi-Jeong; Kim, Ji-Youn; An, Seo-Young; An, Chang-Hyeon; Lee, Sanggyu; Sohn, Wern‐Joo; Lee, Youngkyun

doi:10.1016/j.mod.2017.04.404

Cited by 3 publications

(6 citation statements)

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“…Histology and immunostaining were carried out as described previously (Adhikari et al, ). Hematoxylin and eosin (H&E) and Masson's trichrome staining were used to examine morphological changes in detail (Jung et al, ).…”

Section: Methodsmentioning

confidence: 99%

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An endoplasmic reticulum stress regulator, Tmbim6, modulates secretory stage of mice molar

Aryal

Neupane

Adhikari

et al. 2019

Journal Cellular Physiology

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To understand the role of endoplasmic reticulum (ER)-stress in mice molar development, we studied Tmbim6 that antagonizes the unfolded protein response, using Tmbim6 knockout (KO) mice and in vitro organ cultivation with knocking down using small interfering RNA. During molar development, Tmbim6 is expressed in developing tooth at E14-E16, postnatal0 (PN0), and PN6. Mineral content in Tmbim6 KO enamel was reduced while dentin was slightly increased revealing ultrastructural changes in pattern formation of both enamel and dentin. Moreover, odontoblast differentiation was altered with increased Dspp expression at PN0 followed by altered AMELX localizations at PN5. These results were confirmed by in vitro organ cultivation and showed altered Bmp signaling, proliferation, and actin rearrangement in the presumptive ameloblast and odontoblasts that followed the altered expression of differentiation and ER stress-related signaling molecules at E16.5. Overall, ER stress modulated by Tmbim6 would play important roles in patterned dental hard tissue formation in mice molar within a limited period of development. K E Y W O R D Samelogenesis, dentinogenesis, ER stress, molar development, Tmbim6 knockout

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Section: Methodsmentioning

confidence: 99%

“…A TUNEL assay was performed as described previously (Adhikari et al, ) using an in‐situ cell apoptosis detection kit (cat# 4810‐30‐K; Trevigen, Gaithersburg, MD) according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

An endoplasmic reticulum stress regulator, Tmbim6, modulates secretory stage of mice molar

Aryal

Neupane

Adhikari

et al. 2019

Journal Cellular Physiology

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“…GRHL3 is known to act in regulating the NNE/NE border prior to neurulation, and in epithelial maintenance and EMT in cancer cells, working through similar targets as its family member GRHL2 does during cranial NTC, such as E-Cadherin (E-CAD) and ZO-1. 41,[44][45][46] GRHL2 has also been shown to regulate the transcription of specific claudins in the NNE, 25 and disruption of different claudins can yield regionally specific NTDs in both chick and mouse embryos along the R-C Axis, 51 suggesting that epithelial state could be differentially regulated along the R-C axis.…”

Section: Grhl3 Is Not Required For Patterning Of the Nne Or Ne Or For Maintenance Of Epithelial Integrity During Spinal Neurulationmentioning

confidence: 99%

“…Second, GRHL3 may function in the maintenance of epithelial transcription programs, which it does in other contexts such as cancer cells or barrier formation in the developing epidermis. [44][45][46] Its family member GRHL2 is an important suppressor of epithelial to mesenchymal transitions (EMT), 47,48 including in the cranial NNE, and loss of epithelial properties of the NNE contribute to exencephaly in Grhl2 mutant embryos. 25 Thus, GRHL3 may function in regulating the epithelial properties of the NNE in the caudal regions, similar to GRHL2 in cranial regions.…”

Section: Introductionmentioning

confidence: 99%

Loss of Grhl3 is correlated with altered cellular protrusions in the non‐neural ectoderm during neural tube closure

Jaffe

Niswander

2021

Developmental Dynamics

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Background: The transcription factor Grainyhead-like 3 (GRHL3) has multiple roles in a variety of tissues during development including epithelial patterning and actin cytoskeletal regulation. During neural tube closure (NTC) in the mouse embryo, GRHL3 is expressed and functions in the non-neural ectoderm (NNE). Two important functions of GRHL3 are regulating the actin cytoskeleton during NTC and regulating the boundary between the NNE and neural ectoderm. However, an open question that remains is whether these functions explain the caudally restricted neural tube defect (NTD) of spina bifida observed in Grhl3 mutants. Results: Using scanning electron microscopy and immunofluorescence based imaging on Grhl3 mutants and wildtype controls, we show that GRHL3 is dispensable for NNE identity or epithelial maintenance in the caudal NNE but is needed for regulation of cellular protrusions during NTC. Grhl3 mutants have decreased lamellipodia relative to wildtype embryos during caudal NTC, first observed at the onset of delays when lamellipodia become prominent in wildtype embryos. At the axial level of NTD, half of the mutants show increased and disorganized filopodia and half lack cellular protrusions. Conclusion:These data suggest that altered cellular protrusions during NTC contribute to the etiology of NTD in Grhl3 mutants.

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“…In addition, Grhl3 regulates phosphatase and tensin homolog (PTEN) in squamous cell carcinoma of the skin (Darido et al 2011), and phosphorylated PTEN is expressed throughout the developing oral epithelium (Cho et al 2008), suggestive of possible cooperative regulation in the maintenance of oral epithelial fidelity. Last, Grhl3 has also been shown to regulate Ctnnb1 and Gli3 within the developing circumvellate papillae epithelium (Adhikari et al 2017), indicating that Grhl3-dependent regulation of genes within the Shh pathway, which itself is a critical regulator of maxillofacial development, may underpin craniofacial formation.…”

Section: Further Transcriptional Targets Of Grh/grhl/grhl Genes In Craniofacial Development?mentioning

confidence: 99%

Grainyhead-like Transcription Factors in Craniofacial Development

et al. 2017

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Craniofacial development in vertebrates involves the coordinated growth, migration, and fusion of several facial prominences during embryogenesis, processes governed by strict genetic and molecular controls. A failure in any of the precise spatiotemporal sequences of events leading to prominence fusion often leads to anomalous facial, skull, and jaw formation-conditions termed craniofacial defects (CFDs). Affecting approximately 0.1% to 0.3% of live births, CFDs are a highly heterogeneous class of developmental anomalies, which are often underpinned by genetic mutations. Therefore, identifying novel disease-causing mutations in genes that regulate craniofacial development is a critical prerequisite to develop new preventive or therapeutic measures. The Grainyhead-like ( GRHL) transcription factors are one such gene family, performing evolutionarily conserved roles in craniofacial patterning. The antecedent member of this family, Drosophila grainyhead ( grh), is required for head skeleton development in fruit flies, loss or mutation of Grhl family members in mouse and zebrafish models leads to defects of both maxilla and mandible, and recently, mutations in human GRHL3 have been shown to cause or contribute to both syndromic (Van Der Woude syndrome) and nonsyndromic palatal clefts. In this review, we summarize the current knowledge regarding the craniofacial-specific function of the Grainyhead-like family in multiple model species, identify some of the major target genes regulated by the Grhl transcription factors in craniofacial patterning, and, by examining animal models, draw inferences as to how these data will inform the likely roles of GRHL factors in human CFDs comprising palatal clefting. By understanding the molecular networks regulated by Grhl2 and Grhl3 target genes in other systems, we can propose likely pathways that mediate the effects of these transcription factors in human palatogenesis.

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Grhl3 modulates epithelial structure formation of the circumvallate papilla during mouse development

Cited by 3 publications

References 0 publications

An endoplasmic reticulum stress regulator, Tmbim6, modulates secretory stage of mice molar

An endoplasmic reticulum stress regulator, Tmbim6, modulates secretory stage of mice molar

Loss of Grhl3 is correlated with altered cellular protrusions in the non‐neural ectoderm during neural tube closure

Grainyhead-like Transcription Factors in Craniofacial Development

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