<i>Pitx2-Sox2-Lef1</i> interactions specify progenitor oral/dental epithelial cell signaling centers

Yu, Wenjie; Sun, Zhao; Sweat, Yan Yan; Sweat, Mason; Venugopalan, Shankar Rengasamy; Eliason, Steven; Cao, Huojun; Paine, Michael L.; Amendt, Brad A.

doi:10.1242/dev.186023

Cited by 29 publications

(31 citation statements)

References 55 publications

(82 reference statements)

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“…The molecular identification of the reactivated PITX2 transcriptional complex in cancer is currently unknown; however, it appears that PITX2 requires additional co-factors or interaction partners to transcriptionally regulate its target genes [330][331][332] , as commonly seen in developmental PITX2 signaling with, for example, SOX2 (sex determining region Y-box 2) and LEF1 [333] or FOXC1 (Forkhead box C1) [334] . As mentioned above, the Wnt/β-catenin pathway is not a pre-requisite for PITX2, however, it could be envisaged that coactivation of Wnt/β-catenin is likely to enhance and strengthen PITX2-mediated transcription of ABCB1 in a self-propagating cycle.…”

Section: Pitx2 Regulation Of Abcb1mentioning

confidence: 99%

Teaching an old dog new tricks: reactivated developmental signaling pathways regulate ABCB1 and chemoresistance in cancer

Lee¹,

Totzke²

2021

CDR

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Oncogenic multidrug resistance (MDR) is a multifactorial phenotype intimately linked to deregulated expression of detoxification transporters. Drug efflux transporters, particularly the MDR P-glycoprotein ABCB1, represent a central mechanism by which not only chemotherapeutic drugs are extruded or sequestered to prevent drug delivery to their intracellular targets, but also for inhibiting apoptotic cell death cues, such as removal of proapoptotic signals. Several cell populations exhibiting the MDR phenotype co-exist within a tumor, such as cells forming the bulk tumor cell mass, cancer stem cells, and cancer persister cells. The key to regulation of ABCB1 expression is the cellular transcriptional machinery. Developmental signaling pathways (e.g, Hedgehog, Notch, Wnt/β-catenin, TGFβ, PITX2) are pivotal in governing cell proliferation, survival, differentiation and guiding cell migration during embryogenesis, and their reactivation during carcinogenesis, which is of particular significance for tumor initiation, progression, and metastasis, also leads to the upregulation of ABCB1. These pathways also drive and maintain cancer cell stemness, for which ABCB1 is used as a marker. In this review, the contribution of canonical and non-canonical developmental signaling pathways in transcriptional regulation of ABCB1 to confer MDR in cancer is delineated.

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Section: Pitx2 Regulation Of Abcb1mentioning

confidence: 99%

Teaching an old dog new tricks: reactivated developmental signaling pathways regulate ABCB1 and chemoresistance in cancer

Lee¹,

Totzke²

2021

CDR

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“…Mutations in the Pitx2 are associated with Axenfeld–Rieger Syndrome in humans, which presents with dental anomalies, including hypodontia and enamel hypoplasia [ 47 ]. Sox2 marks a dental epithelial signaling center through interaction with Pitx2 and Lef1 [ 48 ]. Foxi3 [ 49 ], Dlx2 , Lef1 , and p63 may also be responsible for driving dental fate [ 22 ].…”

Section: The Role Of Tfs and Chromatin Regulators In Dental Epithementioning

confidence: 99%

Transcriptional Regulation of Dental Epithelial Cell Fate

Yoshizaki

Fukumoto

Bikle

et al. 2020

IJMS

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Dental enamel is hardest tissue in the body and is produced by dental epithelial cells residing in the tooth. Their cell fates are tightly controlled by transcriptional programs that are facilitated by fate determining transcription factors and chromatin regulators. Understanding the transcriptional program controlling dental cell fate is critical for our efforts to build and repair teeth. In this review, we describe the current understanding of these regulators essential for regeneration of dental epithelial stem cells and progeny, which are identified through transgenic mouse models. We first describe the development and morphogenesis of mouse dental epithelium in which different subpopulations of epithelia such as ameloblasts contribute to enamel formation. Then, we describe the function of critical factors in stem cells or progeny to drive enamel lineages. We also show that gene mutations of these factors are associated with dental anomalies in craniofacial diseases in humans. We also describe the function of the master regulators to govern dental lineages, in which the genetic removal of each factor switches dental cell fate to that generating hair. The distinct and related mechanisms responsible for the lineage plasticity are discussed. This knowledge will lead us to develop a potential tool for bioengineering new teeth.

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“…Pax9 +/− Eda −/− mice also exhibited a mandibular incisor phenotype as 10 of 13 embryos studied lacked lower incisors while in three of 13 embryos only a single mandibular incisor was present. In mouse genetic models disruptions in Pitx2, BCL11B and Wnt, Fgf, Bmp, and Wnt signaling pathway genes result in incisor organ agenesis or hypoplasia (Lin et al, 1999;Lu et al, 1999;Millar et al, 2003;Golonzhka et al, 2009;Yang et al, 2013;Yu et al, 2020). Furthermore, supernumerary incisors arise in mice lacking Spry2/4, Sostdc1, and Lrp4 (Ohazama et al, 2008;Munne et al, 2009;Charles et al, 2011).…”

Section: ; Fraziermentioning

confidence: 99%

Pax9’s Interaction With the Ectodysplasin Signaling Pathway During the Patterning of Dentition

et al. 2020

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In these studies, we explored for the first time the molecular relationship between the paired-domain-containing transcription factor, Pax9, and the ectodysplasin (Eda) signaling pathway during mouse incisor formation. Mice that were deficient in both Pax9 and Eda were generated, and the status of dentition analyzed in all progeny using gross evaluation and histomorphometric means. When compared to wildtype controls, Pax9+/–Eda–/– mice lack mandibular incisors. Interestingly, Fgf and Shh signaling are down-regulated while Bmp4 and Lef1 appear unaffected. These findings suggest that Pax9-dependent signaling involves the Eda pathway and that this genetic relationship is important for mandibular incisor development. Studies of records of humans affected by mutations in PAX9 lead to the congenital absence of posterior dentition but interestingly involve agenesis of mandibular central incisors. The latter phenotype is exhibited by individuals with EDA or EDAR mutations. Thus, it is likely that PAX9, in addition to playing a role in the formation of more complex dentition, is also involved with EDA signaling in the initiation of odontogenesis within the incisal domain.

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Pitx2-Sox2-Lef1 interactions specify progenitor oral/dental epithelial cell signaling centers

Cited by 29 publications

References 55 publications

Teaching an old dog new tricks: reactivated developmental signaling pathways regulate ABCB1 and chemoresistance in cancer

Teaching an old dog new tricks: reactivated developmental signaling pathways regulate ABCB1 and chemoresistance in cancer

Transcriptional Regulation of Dental Epithelial Cell Fate

Pax9’s Interaction With the Ectodysplasin Signaling Pathway During the Patterning of Dentition

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