msx1 regulate

Tooth agenesis is a common structural birth defect in humans that results from failure of morphogenesis during early tooth development. The homeobox transcription factor Msx1 and the canonical Wnt signaling pathway are essential for "bud to cap" morphogenesis and are causal factors for tooth agenesis. Our recent study suggested that Msx1 regulates Wnt signaling during early tooth development by suppressing the expression of Dkk2 and Sfrp2 in the tooth bud mesenchyme, and it demonstrated partial rescue of Msx1 -deficient molar teeth by a combination of DKK inhibition and genetic inactivation of SFRPs...

The osteoblast differentiation capacity of mesenchymal stem cells must be tightly regulated, as inadequate bone mineralization can lead to osteoporosis, and excess bone formation can cause the heterotopic ossification of soft tissues. The balanced protein level of Msh homeobox 1 (MSX1) is critical during normal osteogenesis. To understand the factors that prevent MSX1 protein degradation, the identification of deubiquitinating enzymes (DUBs) for MSX1 is essential. In this study, we performed loss-of-function-based screening for DUBs regulating MSX1 protein levels using the CRISPR/Cas9 system...

Msx1 is essential for the maintenance of the odontogenic fate of dental mesenchymal cells, and is regulated by BMP/Smad1/5 signaling in a Smad4-independent manner. However, the exact co-factors that assist pSmad1/5 entering the nucleus to regulate Msx1 in dental mesenchymal cells are still unknown. Importin7 (IPO7) is one of the important members of importin β-superfamily, which is mainly responsible for nucleocytoplasmic shuttling of RNAs and proteins, including transcription factors. This study aims to investigate whether IPO7 participates in the nuclear translocation of pSmad1/5 activated by BMP4 to regulate Msx1 expression in mouse dental mesenchymal cells...

Development of the secondary palate displays molecular heterogeneity along the anterior-posterior axis; however, the underlying molecular mechanism remains largely unknown. MSX1 is an anteriorly expressed transcription repressor required for palate development. Here, we investigate the role of Msx1 in regional patterning of the secondary palate. The Wnt1-Cre-mediated expression of Msx1 (RosaMsx1Wnt1-Cre ) throughout the palatal mesenchyme leads to cleft palate in mice, associated with aberrant cell proliferation and cell death...

The genome-wide promoter interactome is primarily maintained and regulated by architectural proteins such as CTCF and cohesin. However, some studies suggest a role for non-coding RNAs (ncRNAs) in this process. We aimed to characterise the regulatory role of RNA-mediated promoter interactions in the control of gene expression. We integrated genome-wide datasets of RNA-chromatin and promoter-genome interactions in human embryonic stem cells (hESCs) to identify putative RNA-mediated promoter interactions. We discovered that CTCF sites were enriched in RNA-PIRs (promoter interacting regions co-localising with RNA-chromatin interaction sites) and genes interacting with RNA-PIRs containing CTCF sites showed higher expression levels...

Vascular calcification increases morbidity and mortality in patients with cardiovascular and renal diseases. Previously, we reported that histone deacetylase 1 prevents vascular calcification, whereas its E3 ligase, mouse double minute 2 homolog (MDM2), induces vascular calcification. In the present study, we identified the upstream regulator of MDM2. By utilizing cellular models and transgenic mice, we confirmed that E3 ligase activity is required for vascular calcification. By promoter analysis, we found that both msh homeobox 1 (Msx1) and msh homeobox 2 (Msx2) bound to the MDM2 promoter region, which resulted in transcriptional activation of MDM2...

Skeletal deformities are typical AD-HIES manifestations, which are mainly caused by heterozygous and loss-of-function mutations in Signal transducer and activator of transcription 3 (STAT3). However, the mechanism is still unclear and the treatment strategy is limited. Herein, we reported that the mice with Stat3 deletion in osteoblasts, but not in osteoclasts, induced AD-HIES-like skeletal defects, including craniofacial malformation, osteoporosis, and spontaneous bone fracture. Mechanistic analyses revealed that STAT3 in cooperation with Msh homeobox 1(MSX1) drove osteoblast differentiation by promoting Distal-less homeobox 5(Dlx5) transcription...

OBJECTIVE: To detect the binding of Mage-D1 with activated p75NTR and explore their role in regulating mineralization of ectomesenchymal stem cells (EMSCs). METHODS: EMSCs were isolated from the tooth germs of embryonic SD rats (19.5 days of gestation) by tissue explant culture and were identified for surface markers using flow cytometry. The cultured cells were divided into blank control group, 100 ng/mL nerve growth factor (NGF) stimulation group, and lentivirus-mediated Mage-D1 interference (SH-Mage-D1) group...

BACKGROUND: Development of dental tissue is regulated by extensive cell crosstalk based on various signaling molecules, such as bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) pathways. However, an intact network of the intercellular regulation is still lacking. RESULT: To gain an unbiased and comprehensive view of this dental cell interactome, we applied single-cell RNA-seq on immature human tooth germ of the growing third molar, discovered refined cell subtypes, and applied multiple network analysis to identify the central signaling pathways...

Despite the common application in pregnancy at clinical practice, it remains ambiguous whether dexamethasone (Dex) exposure can affect embryonic myogenesis. In this study, firstly we showed that 10-6 M Dex (Cheng et al., 2016; 2017) treatment resulted in abnormal myogenesis in chicken embryos. Secondly, we demonstrated that 10-6 M Dex-induced abnormality of myogenesis resulted from aberrant cell proliferation, as well as from alteration of the differentiation process from the early stage of somitogenesis up to the late stage of myogenesis...

Deregulation of many homeobox genes has been observed in various cancers and has caused functional implications in the tumor progression. In this review, we will focus on the roles of the human muscle segment homeobox (MSX) transcription factor family in the process of tumorigenesis. The MSX transcription factors, through complex downstream regulation mechanisms, are promoters or inhibitors of diverse cancers by participating in cell proliferation, cell invasion, cell metastasis, cell apoptosis, cell differentiation, drug resistance of tumors, maintenance of tumor stemness, and tumor angiogenesis...

Cutaneous melanoma represents one of the deadliest types of skin cancer. The prognosis strongly depends on the disease stage, thus early detection is crucial. New therapies, including BRAF and MEK inhibitors and immunotherapies, have significantly improved the survival of patients in the last decade. However, intrinsic and acquired resistance is still a challenge. In this review, we discuss two major aspects that contribute to the aggressiveness of melanoma, namely, the embryonic origin of melanocytes and melanoma cells and cellular plasticity...

It is known that genetic factors determine odontogenesis; furthermore, studies have revealed that various genes in humans can regulate the development of different types and generations of teeth. In this study it has been assumed that tooth impaction-at least to some extent-also depends on the presence of specific genetic markers, especially allelic variants of the MSX1 gene. The primary objective of the study was to evaluate the suitability of selected molecular markers located within the MSX1 gene for the determination of the risk of tooth impaction in particular patients...

A recent study from our lab revealed that the inhibition of cyclooxygenase-2 (COX-2) exclusively reduces the level of PGE2 (Prostaglandin E2 ) among prostanoids and hampers the normal development of several structures, strikingly the cranial vault, in chick embryos. In order to unearth the mechanism behind the deviant development of cranial features, the expression pattern of various factors that are known to influence cranial neural crest cell (CNCC) migration was checked in chick embryos after inhibiting COX-2 activity using etoricoxib...

Gonadotropin-releasing hormone (GnRH) is the initial central regulator of the animal reproduction system, which is crucial for puberty onset and fertility. However, the mechanisms regulating GnRH production and release remain unclear. In addition, few studies reported that miR-375 expressed in mouse hypothalamus, but up to now there are limited functional studies of miR-375 in regulating GnRH secretion. According to our recent findings that miR-375 was involved in regulating the synthesis and secretion of pituitary hormones, thus, we aimed to identify the role of miR-375 in regulating GnRH production in GT1-7 cells...

BACKGROUND: Wolf-Hirschhorn (WHS) is a set of congenital physical anomalies and mental retardation associated with a partial deletion of the short arm of chromosome 4. To establish a genotype-phenotype correlation; we carried out a molecular cytogenetic analysis on two Tunisian WHS patients. Patient 1 was a boy of 1-year-old, presented a typical WHS phenotype while patient 2, is a boy of 2 days presented an hypospadias, a micropenis and a cryptorchidie in addition to the typical WHS phenotype...

Like all developmental processes, odontogenesis is highly complex and dynamically regulated, with hundreds of genes co-expressed in reciprocal networks. Tooth agenesis (missing one or more/all teeth) is a common human craniofacial anomaly and may be caused by genetic variations and/or environmental factors. Variants in PAX9, MSX1, AXIN2, EDA, EDAR and WNT10A genes are associated with tooth agenesis. Currently, variants in ATF1, DUSP10, CASC8, IRF6, KDF1, GREM2, LTBP3 and components and regulators of WNT signaling WNT10B, LRP6, DKK, KREMEN1 are at the forefront of interest...

Myogenesis is an important and complicated biological process, especially during the process of embryonic development. The homeoprotein Msx1 is a crucial transcriptional repressor of myogenesis and maintains myogenic precursor cells in an undifferentiated, proliferative state. However, the molecular mechanism through which Msx1 coordinates myogenesis remains to be elucidated. Here, we determine the interacting partner proteins of Msx1 in myoblast cells by a proteomic screening method. Msx1 is found to interact with 55 proteins, among which our data demonstrate that the cooperation of Runt-related transcription factor 1 (Runx1) with Msx1 is required for myoblast cell differentiation...

PURPOSE: Progestin resistance is a critical obstacle for endometrial conservative therapy. Therefore, studies to acquire a more comprehensive understanding of the mechanisms are urgent. However, the pivotal molecules are still unexplored. MATERIALS AND METHODS: We downloaded GSE121367 from the GEO database. The "limma" R language package was applied to identify differentially expressed genes (DEGs). We conducted Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA)...

Mammalian embryonic diapause is a reproductive phenomenon defined by the reversible arrest in blastocyst development and metabolic activity within the uterus which synchronously becomes quiescent to implantation. This natural strategy, evident in over 130 species across eight orders, can temporally uncouple conception from delivery until conditions are favorable for the survival of the mother and newborn. While the maternal endocrine milieu has been shown to be important for this process, the local molecular mechanisms by which the uterus and embryo achieve quiescence, maintain blastocyst survival and then resumes blastocyst activation with subsequent implantation in response to endocrine cues remains unclear...