Fine tuning of Rac1 and RhoA alters cuspal shapes by remolding the cellular geometry

Liu, Liwen; Tang, Qi; Nakamura, Takashi; Suh, Jun-Gyo; Ohshima, Hayato; Jung, Han Sung

doi:10.1038/srep37828

Cited by 18 publications

(35 citation statements)

References 51 publications

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“…Similarly, disruption of the main components of the cytoskeleton‐associated proteins has been found to contribute to the misshaping of the final cusp pattern in mammals . Also, the disturbance of fibronectin, E‐cadherin, or F‐actin distribution in lophodont gerbils has been previously described to contribute to ectopic invagination of inner enamel epithelium . Moreover, the expression of matriptase (ST14), which mediates assembly of adherent junctions, is lost in these epithelial cells, confirming specific changes in cell membranes during cluster cell formation.…”

Section: Discussionmentioning

confidence: 75%

“…This alteration of Na/K‐ATPase activity indicates modifications in membrane function as a possible developmental process responsible for the cell shape changes during enamel ridge formation. Similarly, disruption of the main components of the cytoskeleton‐associated proteins has been found to contribute to the misshaping of the final cusp pattern in mammals . Also, the disturbance of fibronectin, E‐cadherin, or F‐actin distribution in lophodont gerbils has been previously described to contribute to ectopic invagination of inner enamel epithelium .…”

Section: Discussionmentioning

confidence: 91%

“…Similarly, disruption of the main components of the cytoskeleton-associated proteins has been found to contribute to the misshaping of the final cusp pattern in mammals. 32 Also, the disturbance of fibronectin, E-cadherin, or F-actin distribution in lophodont gerbils has been previously described to contribute to ectopic invagination of inner enamel epithelium. 32 F I G U R E 1 3 Na,K-ATPase expression in the cell membrane of tooth germ.…”

Section: Discussionmentioning

confidence: 98%

“…32 Also, the disturbance of fibronectin, E-cadherin, or F-actin distribution in lophodont gerbils has been previously described to contribute to ectopic invagination of inner enamel epithelium. 32 F I G U R E 1 3 Na,K-ATPase expression in the cell membrane of tooth germ. A,A 0 , In the mesial tooth area, the strong expression of Na,K-ATPase is located in the membranes along the inner enamel epithelium toward stellate reticulum in chameleon.…”

Section: Discussionmentioning

confidence: 98%

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Developmental mechanisms driving complex tooth shape in reptiles

Šulcová

Zahradnicek

Dumková

et al. 2019

Developmental Dynamics

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Background In mammals, odontogenesis is regulated by transient signaling centers known as enamel knots (EKs), which drive the dental epithelium shaping. However, the developmental mechanisms contributing to formation of complex tooth shape in reptiles are not fully understood. Here, we aim to elucidate whether signaling organizers similar to EKs appear during reptilian odontogenesis and how enamel ridges are formed. Results Morphological structures resembling the mammalian EK were found during reptile odontogenesis. Similar to mammalian primary EKs, they exhibit the presence of apoptotic cells and no proliferating cells. Moreover, expression of mammalian EK‐specific molecules (SHH, FGF4, and ST14) and GLI2‐negative cells were found in reptilian EK‐like areas. 3D analysis of the nucleus shape revealed distinct rearrangement of the cells associated with enamel groove formation. This process was associated with ultrastructural changes and lipid droplet accumulation in the cells directly above the forming ridge, accompanied by alteration of membranous molecule expression (Na/K‐ATPase) and cytoskeletal rearrangement (F‐actin). Conclusions The final complex shape of reptilian teeth is orchestrated by a combination of changes in cell signaling, cell shape, and cell rearrangement. All these factors contribute to asymmetry in the inner enamel epithelium development, enamel deposition, ultimately leading to the formation of characteristic enamel ridges.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

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Developmental mechanisms driving complex tooth shape in reptiles

Šulcová

Zahradnicek

Dumková

et al. 2019

Developmental Dynamics

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“…During tooth development, Twist1 is expressed in the mesenchyme, and mesenchymal-conditional Twist1-KO mice show an inhibition of odontoblast differentiation caused by the inhibition of epithelial-mesenchymal interactions (23). In Epfn-KO mice, the dental epithelial cells failed to polarize, and after the bell stage, the immature dental epithelium randomly invades into the mesenchymal region to form multiple teeth (7,9,31). In the present study, we demonstrated that the AmeloD expression in the invading dental epithelial cells of Epfn-KO teeth caused abnormal migration of epithelial cells through partial EMT processes (Fig.…”

Section: Discussionmentioning

confidence: 99%

The transcription factor AmeloD stimulates epithelial cell motility essential for tooth morphology

Chiba

Yoshizaki

et al. 2019

Journal of Biological Chemistry

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The development of ectodermal organs, such as teeth, requires epithelial-mesenchymal interactions. Basic helixloop-helix (bHLH) transcription factors regulate various aspects of tissue development, and we have previously identified a bHLH transcription factor, AmeloD, from a tooth germ cDNA library. Here, we provide both in vitro and in vivo evidence that AmeloD is important in tooth development. We created AmeloD-knockout (KO) mice to identify the in vivo functions of AmeloD that are critical for tooth morphogenesis. We found that AmeloD-KO mice developed enamel hypoplasia and small teeth because of increased expression of E-cadherin in inner enamel epithelial (IEE) cells, and it may cause inhibition of the cell migration. We used the CLDE dental epithelial cell line to conduct further mechanistic analyses to determine whether AmeloD overexpression in CLDE cells suppresses E-cadherin expression and promotes cell migration. Knockout of epiprofin (Epfn), another transcription factor required for tooth morphogenesis and development, and analysis of AmeloD expression and deletion revealed that AmeloD also contributed to multiple tooth formation in Epfn-KO mice by promoting the invasion of dental epithelial cells into the mesenchymal region. Thus, AmeloD appears to play an important role in tooth morphogenesis by modulating E-cadherin and dental epithelial-mesenchymal interactions. These findings provide detailed insights into the mechanism of ectodermal organ development. Ectodermal organs, such as teeth, all display a need for epithelial-mesenchymal interactions for their development. Tooth development is, in fact, a good model for understanding the mechanism of ectodermal development because it has welldefined stages and distinctive differentiated cell types (1). In the mouse, the morphogenesis of the molars is divided into four stages: the initiation stage (embryonic day 11.5 (E11.5)), 2 bud stage (E13.5), cap stage (E15.5), and bell stage (E17.5). At the initiation stage, the dental epithelium starts to thicken and invades into the mesenchymal region. This invagination process forms the tooth bud, and the dental epithelium condenses at the bud stage. After the cap stage, the dental epithelial stem cells differentiate into various cell types to form the enamel organ: the inner enamel epithelium (IEE), outer enamel epithelium, stratum intermedium (SI), and stellate reticulum. The IEE cells are ameloblast progenitor cells, a unique cell population in the proliferation stage as they express proliferation markers but do not express E-cadherin, a negative regulator of cell division and migration (2, 3). The IEE cells actively proliferate and migrate to form a correctly sized enamel organ. After proliferation, the IEE cells differentiate into enamel-secreting ameloblasts. Proliferative IEE cells persist near the apical tip of the

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Structural basis for the distinct roles of non-conserved Pro116 and conserved Tyr124 of BCH domain of yeast p50RhoGAP

Shankar,

Chew,

Chichili

et al. 2024

Cell. Mol. Life Sci.

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Abstractp50RhoGAP is a key protein that interacts with and downregulates the small GTPase RhoA. p50RhoGAP is a multifunctional protein containing the BNIP-2 and Cdc42GAP Homology (BCH) domain that facilitates protein–protein interactions and lipid binding and the GAP domain that regulates active RhoA population. We recently solved the structure of the BCH domain from yeast p50RhoGAP (YBCH) and showed that it maintains the adjacent GAP domain in an auto-inhibited state through the β5 strand. Our previous WT YBCH structure shows that a unique kink at position 116 thought to be made by a proline residue between alpha helices α6 and α7 is essential for the formation of intertwined dimer from asymmetric monomers. Here we sought to establish the role and impact of this Pro116. However, the kink persists in the structure of P116A mutant YBCH domain, suggesting that the scaffold is not dictated by the proline residue at this position. We further identified Tyr124 (or Tyr188 in HBCH) as a conserved residue in the crucial β5 strand. Extending to the human ortholog, when substituted to acidic residues, Tyr188D or Tyr188E, we observed an increase in RhoA binding and self-dimerization, indicative of a loss of inhibition of the GAP domain by the BCH domain. These results point to distinct roles and impact of the non-conserved and conserved amino acid positions in regulating the structural and functional complexity of the BCH domain.

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Fine tuning of Rac1 and RhoA alters cuspal shapes by remolding the cellular geometry

Cited by 18 publications

References 51 publications

Developmental mechanisms driving complex tooth shape in reptiles

Developmental mechanisms driving complex tooth shape in reptiles

The transcription factor AmeloD stimulates epithelial cell motility essential for tooth morphology

Structural basis for the distinct roles of non-conserved Pro116 and conserved Tyr124 of BCH domain of yeast p50RhoGAP

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