scholarly journals Lmx1b influences correct post-mitotic coding of mesodiencephalic dopaminergic neurons

2018 ◽  
Author(s):  
Iris Wever ◽  
Pablo Largo Barrientos ◽  
Elisa J. Hoekstra ◽  
Marten P. Smidt
Keyword(s):  
Transcription Factor ◽  
Dopaminergic Neurons ◽  
Cell Types ◽  
Late Development ◽  
Genetic Ablation ◽  
Depth Analysis ◽  
Homeobox Transcription Factor ◽  
Different Cell Types ◽  
Transcription Factor 1 ◽  
Inductive Activity

AbstractThe Lim Homeobox transcription factor 1 beta (LMX1b) has been identified as one of the transcription factors important for the development of mesodiencephalic dopaminergic (mdDA) neurons. During early development, Lmx1b is essential for induction and maintenance of the Isthmic Organizer (IsO), and genetic ablation results in the disruption of inductive activity from the IsO and loss of properly differentiated mdDA neurons.To study the downstream targets of Lmx1b without affecting the IsO, we generated a conditional model in which Lmx1b was selectively deleted in Pitx3 expressing cells from embryonic day (E)13 onward. Supporting previous data, no significant changes could be observed in general dopamine (DA) marks, like Th, Pitx3 and Vmat2 at E14.5. However, in depth analysis by means of RNA-sequencing revealed that Lmx1b is important for the expression level of survival factors En1 and En2 and for the repression of mdDA subset mark Ahd2 during (late) development. Interestingly, the regulation of Ahd2 by Lmx1b was found to be Pitx3 independent, since Pitx3 levels were not altered in Lmx1b conditional knock-outs (cKO) and Ahd2 expression was also up-regulated in Lmx1b/Pitx3 double mutants compared to Pitx3 mutants. Further analysis of Lmx1b cKOs showed that post-mitotic deletion of Lmx1b additional leads to a loss of TH+ cells at 3 months age both in the VTA and SNc. Remarkably, different cell types were affected in the SNc and the VTA. While TH+AHD2+ cells were lost the SNc, TH+AHD2- neurons were affected in the VTA, reflected by a loss of Cck expression, indicating that Lmx1b is important for the survival of a sub-group of mdDA neurons.

scholarly journals Repression of Virus-Induced Interferon A Promoters by Homeodomain Transcription Factor Ptx1

2000 ◽  
Vol 20 (20) ◽  
pp. 7527-7540 ◽  
Author(s):  
Sébastien Lopez ◽  
Marie-Laure Island ◽  
Jacques Drouin ◽  
Marie-Thérese Bandu ◽  
Nicolas Christeff ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Differential Expression ◽  
Antisense Rna ◽  
Differentially Express ◽  
Regulatory Element ◽  
Cell Types ◽  
Functional Feature ◽  
Homeodomain Transcription Factor ◽  
Responsive Element ◽  
Different Cell Types

ABSTRACT Interferon A (IFN-A) genes are differentially expressed after virus induction. The differential expression of individual IFN-A genes is modulated by substitutions in the proximal positive virus responsive element A (VRE-A) of their promoters and by the presence or absence of a distal negative regulatory element (DNRE). The functional feature of the DNRE is to specifically act by repression of VRE-A activity. With the use of the yeast one-hybrid system, we describe here the identification of a specific DNRE-binding protein, the pituitary homeobox 1 (Ptx1 or Pitx1). Ptx1 is detectable in different cell types that differentially express IFN-A genes, and the endogenous Ptx1 protein binds specifically to the DNRE. Upon virus induction, Ptx1 negatively regulates the transcription of DNRE-containing IFN-A promoters, and the C-terminal region, as well as the homeodomain of the Ptx1 protein, is required for this repression. After virus induction, the expression of the Ptx1 antisense RNA leads to a significant increase of endogenous IFN-A gene transcription and is able to modify the pattern of differential expression of individual IFN-A genes. These studies suggest that Ptx1 contributes to the differential transcriptional strength of the promoters of different IFN-A genes and that these genes may provide new targets for transcriptional regulation by a homeodomain transcription factor.

scholarly journals Vascular Calcification in Chronic Kidney Disease: Diversity in the Vessel Wall

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 404
Author(s):  
Prabhatchandra Dube ◽  
Armelle DeRiso ◽  
Mitra Patel ◽  
Dhanushya Battepati ◽  
Bella Khatib-Shahidi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Complex Process ◽  
Cardiovascular Morbidity And Mortality ◽  
Depth Analysis ◽  
Multiple Cell ◽  
Different Cell Types

Vascular calcification (VC) is one of the major causes of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). VC is a complex process expressing similarity to bone metabolism in onset and progression. VC in CKD is promoted by various factors not limited to hyperphosphatemia, Ca/Pi imbalance, uremic toxins, chronic inflammation, oxidative stress, and activation of multiple signaling pathways in different cell types, including vascular smooth muscle cells (VSMCs), macrophages, and endothelial cells. In the current review, we provide an in-depth analysis of the various kinds of VC, the clinical significance and available therapies, significant contributions from multiple cell types, and the associated cellular and molecular mechanisms for the VC process in the setting of CKD. Thus, we seek to highlight the key factors and cell types driving the pathology of VC in CKD in order to assist in the identification of preventative, diagnostic, and therapeutic strategies for patients burdened with this disease.

Expression of Thyroid Transcription Factor-1 and Other Markers in Sclerosing Hemangioma of the Lung

2001 ◽  
Vol 125 (10) ◽  
pp. 1335-1339 ◽  
Author(s):  
Peter B. Illei ◽  
Juan Rosai ◽  
David S. Klimstra
Keyword(s):  
Transcription Factor ◽  
Tumor Cells ◽  
Alveolar Epithelium ◽  
Cell Types ◽  
Pulmonary Epithelium ◽  
Epithelial Tumor ◽  
Sclerosing Hemangioma ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1

Abstract Context.—Sclerosing hemangioma of the lung is well characterized histologically, but the line of differentiation expressed by the tumor cells has been unclear. Despite the implication by its name of a vascular neoplasm, sclerosing hemangioma is considered by most authorities to be an epithelial tumor, possibly related to the pulmonary epithelium. Objectives.—To determine the line of differentiation of the tumor cells with immunohistochemistry and to review the related literature. Design.—Nine cases of histologically typical pulmonary sclerosing hemangioma were studied with pan-epithelial (epithelial membrane antigen [EMA] and CAM 5.2), endothelial (CD31), neuroendocrine (chromogranin A), and pulmonary epithelial markers (thyroid transcription factor-1 and PE10). Staining intensity was separately evaluated in the pale cells of the solid areas and the cells lining the papillary structures. Results.—Both cell types were positive for thyroid transcription factor-1 and EMA in all cases (100%). Thyroid transcription factor-1 showed diffuse strong staining, and EMA staining varied from focal weak to diffuse strong. The pale cells showed focal staining for keratin (CAM 5.2) in 2 (28%) of 7 cases, and for PE10 in 5 (62%) of 8 cases. The papillary lining cells were at least focally positive with CAM 5.2 and PE10 in all cases (100%). Reactions for chromogranin and CD31 were negative in both cell types in every case. The number of PE10- or CAM 5.2–positive papillary lining cells was less than the number of EMA-positive papillary lining cells. Conclusion.—The uniform positivity for EMA is consistent with the notion that the tumor cells of sclerosing hemangioma are epithelial, and the strong thyroid transcription factor-1 positivity suggests differentiation toward pulmonary epithelium. The papillary lining cells expressing EMA as well as PE10 or CAM 5.2 likely represent entrapped metaplastic alveolar epithelium, whereas the papillary lining cells expressing only EMA more likely constitute true neoplastic cells similar to those in the solid areas.

scholarly journals HIV-2/SIV Vpx antagonises NF-𝜅B activation by targeting p65

2021 ◽  
Author(s):  
Douglas L Fink ◽  
James Cai ◽  
Matthew VX Whelan ◽  
Christopher Monit ◽  
Carlos Maaluquer de Motes ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Immune Responses ◽  
Gene Networks ◽  
Nuclear Translocation ◽  
Cell Types ◽  
Viral Pathogen ◽  
Mona Monkey ◽  
Molecular Patterns ◽  
Different Cell Types

The NF-𝜅B family of transcription factors and associated signalling pathways are abundant and ubiquitous in human immune responses. Activation of NF-𝜅B transcription factors by viral pathogen-associated molecular patterns, such as viral RNA and DNA, is fundamental to anti-viral innate immune defences and pro-inflammatory cytokine production that steers adaptive immune responses. Diverse non-viral stimuli, such as lipopolysaccharide and cytokines, also activate NF-𝜅B and the same anti-pathogen gene networks. Viruses adapted to human cells often encode multiple proteins aimed at varied NF-𝜅B pathway targeted to mitigate the anti-viral effects of NF-𝜅B-dependent host immunity. In this study we have demonstrated using numerous assays, in a number of different cell types, that plasmid-encoded or virus-delivered Simian Immunodeficiency Virus (SIV) accessory protein Vpx is a broad antagonist of NF-𝜅B signalling active against diverse innate NF-𝜅B agonists. Using targeted Vpx mutagenesis, we showed that this novel Vpx phenotype is independent of known Vpx cofactor DCAF1 and other cellular binding partners, including SAMHD1, STING and the HUSH complex. We found that Vpx co-immunoprecipitated with canonical NF-𝜅B transcription factor p65 and not NF-𝜅B transcription factor proteins p50 or p100, preventing nuclear translocation of p65, a novel mechanism of NF-𝜅B antagonism by lentiviruses. We found that broad antagonism of NF-𝜅B activation by Vpx was conserved across distantly related lentiviruses as well as for Vpr from SIV Mona monkey (SIVmon), which has Vpx-like SAMHD1-degradation activity.

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