Journal ArticleDOI
Grhl3 modulates epithelial structure formation of the circumvallate papilla during mouse development.
Nirpesh Adhikari,Sanjiv Neupane,Gi-Jeong Gwon,Ji-Youn Kim,Chang-Hyeon An,Sanggyu Lee,Wern-Joo Sohn,Youngkyun Lee,Jae-Young Kim +8 more
TLDR
It is proposed that developmental stage-specific Grhl3 plays a significant role in CVP morphogenesis not by just disruption of epithelial integrity but by regulating epithelial cell proliferation, apoptosis, and migration via Shh, Wnt, and apoptosis signaling during mouse embryogenesis.Abstract:
Grainyhead-like 3 (Grhl3) is a transcription factor involved in epithelial morphogenesis. In the present study, we evaluated the developmental role of Grhl3 in structural formation of the circumvallate papilla (CVP), which undergoes dynamic morphological changes during organogenesis. The specific expression pattern of Grhl3 was examined in the CVP-forming region, specifically in the apex and epithelial stalk from E13.5 to E15.5 using in situ hybridization. To determine the role of Grhl3 in epithelial morphogenesis of the CVP, we employed an in vitro tongue culture method, wherein E13.5 tongue were isolated and cultured for 2 days after knocking down of Grhl3. Knockdown of Grhl3 resulted in significant changes to the epithelial structure of the CVP, such that the apical region of the CVP was smaller in size, and the epithelial stalks were more deeply invaginated. To define the mechanisms underlying these morphological alterations, we examined cell migration, proliferation, and apoptosis using phalloidin staining, immunohistochemistry against Ki67, ROCK1, and E-cadherin, and a TUNEL assay, respectively. These results revealed an increase in proliferation, a reduction in apoptosis, and an altered pattern of cytoskeletal formation in the CVP-forming epithelium, following Grhl3 knockdown. In addition, there were changes in the specific expression patterns of signaling and apoptosis-related molecules such as Axin2, Bak1, Bcl2, Casp3, Casp8, Ctnnb1, Cnnd1, Gli3, Lef1, Ptch1, Rock1, Shh, and Wnt11, which could explain the altered cellular and morphological events. Based on these results, we propose that developmental stage-specific Grhl3 plays a significant role in CVP morphogenesis not by just disruption of epithelial integrity but by regulating epithelial cell proliferation, apoptosis, and migration via Shh, Wnt, and apoptosis signaling during mouse embryogenesis.read more
Citations
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Journal ArticleDOI
Structural basis of gene regulation by the Grainyhead/CP2 transcription factor family.
Qianqian Ming,Yvette Roske,Anja Schuetz,Katharina Walentin,Ibraim Ibraimi,Kai M. Schmidt-Ott,Kai M. Schmidt-Ott,Udo Heinemann,Udo Heinemann +8 more
TL;DR: The structural basis of DNA target-site recognition by Grh transcription factors is established and how tumor-associated mutations inactivate Grhl proteins is revealed, which may serve as points of departure for the structure-based development of Grh/CP2 inhibitors for therapeutic applications.
Journal ArticleDOI
In focus in HCB.
Douglas J. Taatjes,Jürgen Roth +1 more
TL;DR: Taking all of the data into consideration, it is recommended that DNase I and citrate buffer may offer less harsh alternatives to hydrochloric acid for DNA denaturation in the BrdU staining protocol.
Journal ArticleDOI
Mis-expression of grainyhead-like transcription factors in zebrafish leads to defects in enveloping layer (EVL) integrity, cellular morphogenesis and axial extension
TL;DR: This study ascribes novel roles to the Grhl family in the context of embryonic development and morphogenesis by utilising the zebrafish to differentially regulate expression of family members grhl2b and grhl3.
Journal ArticleDOI
Grainyhead-like Transcription Factors in Craniofacial Development.
TL;DR: By understanding the molecular networks regulated by Grhl2 and Grhl3 target genes in other systems, it is proposed that likely pathways that mediate the effects of these transcription factors in human palatogenesis are proposed.
Journal ArticleDOI
Spotlight on the Granules (Grainyhead-Like Proteins) - From an Evolutionary Conserved Controller of Epithelial Trait to Pioneering the Chromatin Landscape.
TL;DR: The essential roles of grh and GRHL factors during embryogenesis and pathogenesis are highlighted, with a special focus on its emerging pioneering function.
References
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TL;DR: These findings identify a cell-autonomous defect of convergent extension, requiring PCP signalling via RhoA-Rho kinase, during the development of severe neural tube defects in the mouse.
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