Topic
NFIC
About: NFIC is a research topic. Over the lifetime, 68 publications have been published within this topic receiving 1682 citations.
Papers published on a yearly basis
Papers
TL;DR: An estrogen-regulated combinatorial network including cell-specific cis- and trans-regulators of CCND1 expression where ERalpha collaborates with other transcription factors associated with the ER-positive breast cancer phenotype, including FoxA1 and NFIC is revealed.
Abstract: Estrogen stimulates the proliferation of the most common type of human breast cancer that expresses estrogen receptor α (ERα) through the activation of the cyclin D1 (CCND1) oncogene. However, our knowledge of ERα transcriptional mechanisms remains limited. Hence, it is still elusive why ERα ectopically expressed in ER-negative breast cancer cells (BCC) is functional on ectopic reporter constructs but lacks activity on many endogenous target genes, including CCND1. Here, we show that estradiol (E2) stimulation of CCND1 expression in BCC depends on a novel cell-type-specific enhancer downstream from the CCND1 coding region, which is the primary ERα recruitment site in estrogen-responsive cells. The pioneer factor FoxA1 is specifically required for the active chromatin state of this enhancer and as such is crucial for both CCND1 expression and subsequent cell cycle progression. Interestingly, even in BCC, CCND1 levels and proliferation are tightly controlled by E2 through the establishment of a negative feedforward loop involving the induction of NFIC, a putative tumor suppressor capable of directly repressing CCND1 transcription. Taken together, our results reveal an estrogen-regulated combinatorial network including cell-specific cis- and trans-regulators of CCND1 expression where ERα collaborates with other transcription factors associated with the ER-positive breast cancer phenotype, including FoxA1 and NFIC.
314 citations
TL;DR: This study has revealed an important signaling mechanism in which TGF‐β/BMP signaling relies on a Smad‐dependent mechanism in regulating Nfic expression via Shh signaling to control root development.
Abstract: Transforming growth factor beta (TGF-beta)/bone morphogenetic protein (BMP) signaling is crucial for regulating epithelial-mesenchymal interaction during organogenesis, and the canonical Smad pathway-mediated TGF-beta/BMP signaling plays important roles during development and disease. During tooth development, dental epithelial cells, known as Hertwig's epithelial root sheath (HERS), participate in root formation following crown development. However, the functional significance of HERS in regulating root development remains unknown. In this study we investigated the signaling mechanism of Smad4, the common Smad for TGF-beta/BMP signaling, in HERS in regulating root development. Tissue-specific inactivation of Smad4 in HERS results in abnormal enamel and dentin formation in K14-Cre;Smad4(fl/fl) mice. HERS enlarges but cannot elongate to guide root development without Smad4. At the molecular level, Smad4-mediated TGF-beta/BMP signaling is required for Shh expression in HERS and Nfic (nuclear factor Ic) expression in the cranial neural crest (CNC)-derived dental mesenchyme. Nfic is crucial for root development, and loss of Nfic results in a CNC-derived dentin defect similar to the one of K14-Cre;Smad4(fl/fl) mice. Significantly, we show that ectopic Shh induces Nfic expression in dental mesenchyme and partially rescues root development in K14-Cre;Smad4(fl/fl) mice. Taken together, our study has revealed an important signaling mechanism in which TGF-beta/BMP signaling relies on a Smad-dependent mechanism in regulating Nfic expression via Shh signaling to control root development. The interaction between HERS and the CNC-derived dental mesenchyme may guide the size, shape, and number of tooth roots.
150 citations
TL;DR: It is shown that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis, underscoring importance of the PTHrP–PPR system during root morphogenesis and tooth eruption.
Abstract: Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP-PPR system during root morphogenesis and tooth eruption.
123 citations
TL;DR: The results indicate that the loss of Nfic leads to the suppression of odontogenic cell proliferation and differentiation and induces apoptosis of aberrant odontoblasts during root formation, thereby contributing to the formation of short roots.
109 citations
TL;DR: The loss of Nfic caused disrupted odontoblast differentiation, which resulted in the formation of short and abnormal roots, and decreased cementum, which suggests that root dentin is required for normal cementum formation.
Abstract: Background: Nuclear factor I genes play an important role in the development of the brain, lung, and roots of teeth. We had reported that Nfic-deficient mice form normal crowns, but abnormal roots of molar teeth. However, the mechanism by which the disruption of Nfic gene causes abnormal root formation remains unknown. Methods: To understand this mechanism, the root formation in Nfic-deficient mice was examined and compared to that of wild-type mice by morphological, immunohistochemical, and in situ hybridization analyses. Results: Nfic-deficient mice formed normal Hertwig's epithelial root sheath (HERS) but severely disrupted odontoblast differentiation, leading to the formation of aberrant odontoblasts in the early stage of root formation. They became dissociated and polygonal in shape, lost their orientation and polarity, and did not express dentin sialophosphoprotein. The abnormal roots contained trapped aberrant odontoblasts, thereby resembling osteodentin in overall morphology. No osteoclasts were associated with abnormal roots. Further, the abnormal roots exhibited a decreased number of cementoblasts and cementum formation on the root surface. Conclusions: The loss of Nfic did not interfere with the formation of HERS, but it caused disrupted odontoblast differentiation, which resulted in the formation of short and abnormal roots, and decreased cementum. This finding suggests that root dentin is required for normal cementum formation. Therefore, Nfic may be a key regulator of root odontoblast differentiation and root formation.
80 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 10 |
| 2020 | 7 |
| 2019 | 3 |
| 2018 | 3 |
| 2017 | 5 |
| 2016 | 3 |