Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal

Sun, Zhao; Yu, Wenjie; Sanz-Navarro, Maria; Sweat, Mason; Eliason, Steven; Sharp, Thomas E; Liu, Huan; Seidel, Kerstin; Zhang, Li; Moreno, Myriam; Lynch, Thomas J.; Holton, Nathan E.; Rogers, Laura M.; Neff, T.; Goodheart, Michael J.; Michon, Frédéric; Klein, Ophir D.; Chai, Yang; Dupuy, Adam J.; Engelhardt, John F.; Chen, Zhi; Amendt, Brad A.

doi:10.1242/dev.138883

Cited by 57 publications

(121 citation statements)

References 49 publications

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“…Following the standard immunostaining process, sections were treated with 2 M HCl for 1 h and neutralized with 1×PBS. Detailed IdU/CIdU labeling processes could be found in our previous paper (Sun et al, 2016). …”

Section: Methodsmentioning

confidence: 99%

Irx1 regulates dental outer enamel epithelial and lung alveolar type II epithelial differentiation

Eliason

et al. 2017

Developmental Biology

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The Iroquois genes (Irx) appear to regulate fundamental processes that lead to cell proliferation, differentiation, and maturation during development. In this report, the Iroquois homeobox 1 (Irx1) transcription factor was functionally disrupted using a LacZ insert and LacZ expression demonstrated stage-specific expression during embryogenesis. Irx1 is highly expressed in the brain, lung, digits, kidney, testis and developing teeth. Irx1 null mice are neonatal lethal and this lethality it due to pulmonary immaturity. Irx1−/− mice show delayed lung maturation characterized by defective surfactant protein secretion and Irx1 marks a population of SP-C expressing alveolar type II cells. Irx1 is specifically expressed in the outer enamel epithelium (OEE), stellate reticulum (SR) and stratum intermedium (SI) layers of the developing tooth. Irx1 mediates dental epithelial cell differentiation in the lower incisors resulting in delayed growth of the lower incisors. Irx1 is specifically and temporally expressed during developmental stages and we have focused on lung and dental development in this report. Irx1+ cells are unique to the development of the incisor outer enamel epithelium, patterning of Lef-1+ and Sox2+ cells as well as a new marker for lung alveolar type II cells. Mechanistically, Irx1 regulates Foxj1 and Sox9 to control cell differentiation during development.

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Section: Methodsmentioning

confidence: 99%

Irx1 regulates dental outer enamel epithelial and lung alveolar type II epithelial differentiation

Eliason

et al. 2017

Developmental Biology

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“…One major difference between teeth and other odontodes appears to be expression of Sox2 in teeth, which establishes epithelial progenitor cells with regenerative capabilities that are unique to teeth . The importance of Sox2 in stem cell maintenance, especially in dental epithelial stem cells, has been broadly demonstrated in teeth of mammals, reptiles, and fish, providing evidence for the deep homology of tooth patterning mechanisms regardless of the origin of epithelial tissue.…”

Section: Dental Stem Cell Origins Development and Maintenance Are Rmentioning

confidence: 99%

Tissue Mechanical Forces and Evolutionary Developmental Changes Act Through Space and Time to Shape Tooth Morphology and Function

Calamari

Klein

2018

BioEssays

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Efforts from diverse disciplines, including evolutionary studies and biomechanical experiments, have yielded new insights into the genetic, signaling, and mechanical control of tooth formation and functions. Evidence from fossils and non-model organisms has revealed that a common set of genes underlie tooth-forming potential of epithelia, and changes in signaling environments subsequently result in specialized dentitions, maintenance of dental stem cells, and other phenotypic adaptations. In addition to chemical signaling, tissue forces generated through epithelial contraction, differential growth, and skeletal constraints act in parallel to shape the tooth throughout development. Here we review recent advances in understanding dental development from these studies and discuss important gaps that can be filled through continued application of evolutionary and biomechanical approaches.

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“…It was reported by multiple groups that Lef-1 is a marker for enamel knot in teeth (Jernvall et al, 1998;Kratochwil et al, 1996;Sasaki et al, 2005;Sun et al, 2016b).…”

Section: Dental Epithelial Signaling Centers In Tooth Developmentmentioning

confidence: 99%

“…Following the standard immunostaining process, sections were treated with 2M HCl for 1 hour and neutralized with 1×PBS. Detailed IdU/CIdU labeling processes could be found in our previous paper (Sun et al, 2016a).…”

Section: Brdu Cidu and Idu Labelingmentioning

confidence: 99%

“…Since the Cre recombinase in the Shh-Cre mouse is only expressed in the anterior part of molars and incisors, Sox2 was not fully ablated in the teeth of Shh Cre Sox2 f/f mice(Juuri et al, 2013). I have studied the function of Sox2 in tooth development and adult incisor maintenance in Pitx2 Cre Sox2 f/f mice, in which Sox2 was totally ablated by the expression of Pitx2-drived Cre recombinase(Sun et al, 2016b). I found that Sox2 and…”

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A Pitx2-Irx1 regulatory network controls dental epithelial stem cell differentiation during tooth development

Yu¹

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Dental disorders are one of the most common developmental defects in humans. During tooth development, cell patterning, morphogenesis, and differentiation are fundamental processes, which are mediated by conserved signaling pathways and transcription factors. Genetic mutations in regulators of these pathways often lead to developmental defects in teeth. For example, individuals with DiGeorge syndrome have dental abnormalities caused by mutations in T-box protein 1 (TBX1), a gene that regulates tooth development. Although more than 300 genes have been associated with tooth development, the underlying mechanisms remains elusive. In this dissertation, I studied the function of Pituitary homeobox 2 (Pitx2) and Iroquois 1 (Irx1) in mice. I showed that Pitx2 controls dental epithelial stem cell (DESC) differentiation and proliferation at early stages of tooth development. Additionally, I found that Irx1 regulates the differentiation of DESCs to outer enamel epithelium (OEE) at the later stage of tooth development. The regulation of Pitx2 is partially through sonic hedgehog (Shh) signaling, which is produced by the dental epithelial signaling center and critical for tooth development. In addition, I show that Pitx2 directly promotes the expression of Irx1, and then regulates the expression of Forkhead box protein J1 (Foxj1) and Sex determining region Y-box9 (Sox9). In this dissertation, I show that the Pitx2-Irx1 regulatory network is essential for tooth development with evidence at the cellular and molecular level. The findings of my study provide the field with a better understanding of the underlying mechanisms of tooth development and regeneration. viii TABLE OF CONTENTS LIST OF FIGURES .

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Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal

Cited by 57 publications

References 49 publications

Irx1 regulates dental outer enamel epithelial and lung alveolar type II epithelial differentiation

Irx1 regulates dental outer enamel epithelial and lung alveolar type II epithelial differentiation

Tissue Mechanical Forces and Evolutionary Developmental Changes Act Through Space and Time to Shape Tooth Morphology and Function

A Pitx2-Irx1 regulatory network controls dental epithelial stem cell differentiation during tooth development

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