R8 development in theDrosophilaeye: a paradigm for neural selection and differentiation

Development ◽  
2002 ◽  
Vol 129 (6) ◽  
pp. 1295-1306 ◽  
Author(s):  
Benjamin J. Frankfort ◽  
Graeme Mardon
Keyword(s):  
Transcription Factors ◽  
Ganglion Cell ◽  
Signaling Pathways ◽  
Neural Differentiation ◽  
Eye Development ◽  
Developmental Control ◽  
Complex Process ◽  
Mammalian Retina ◽  
Neural Specification ◽  
Neural Selection

The Drosophila eye is an outstanding model with which to decipher mechanisms of neural differentiation. Paramount to normal eye development is the organized selection and differentiation of a patterned array of R8 photoreceptors – the founding photoreceptor of each ommatidium that coordinates the incorporation of all other photoreceptors. R8 development is a complex process that requires the integration of transcription factors and signaling pathways, many of which are highly conserved and perform similar functions in other species. This article discusses the developmental control of the four key elements of R8 development: selection, spacing, differentiation and orchestration of later events. New questions that have surfaced because of recent advances in the field are addressed, and the unique characteristics of R8 development are highlighted through comparisons with neural specification in other Drosophila tissues and with ganglion cell development in the mammalian retina.

scholarly journals Role of Signal Transduction Pathways and Transcription Factors in Cartilage and Joint Diseases

2020 ◽  
Vol 21 (4) ◽  
pp. 1340 ◽  
Author(s):  
Riko Nishimura ◽  
Kenji Hata ◽  
Yoshifumi Takahata ◽  
Tomohiko Murakami ◽  
Eriko Nakamura ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Transcription Factors ◽  
Signaling Pathways ◽  
Genetic Disorder ◽  
Interleukin 1 ◽  
Genetic Diseases ◽  
Mtor Inhibitors ◽  
Joint Diseases ◽  
Ectopic Ossification ◽  
Parathyroid Hormone Related Protein

Osteoarthritis and rheumatoid arthritis are common cartilage and joint diseases that globally affect more than 200 million and 20 million people, respectively. Several transcription factors have been implicated in the onset and progression of osteoarthritis, including Runx2, C/EBPβ, HIF2α, Sox4, and Sox11. Interleukin-1 β (IL-1β) leads to osteoarthritis through NF-ĸB, IκBζ, and the Zn2+-ZIP8-MTF1 axis. IL-1, IL-6, and tumor necrosis factor α (TNFα) play a major pathological role in rheumatoid arthritis through NF-ĸB and JAK/STAT pathways. Indeed, inhibitory reagents for IL-1, IL-6, and TNFα provide clinical benefits for rheumatoid arthritis patients. Several growth factors, such as bone morphogenetic protein (BMP), fibroblast growth factor (FGF), parathyroid hormone-related protein (PTHrP), and Indian hedgehog, play roles in regulating chondrocyte proliferation and differentiation. Disruption and excess of these signaling pathways cause genetic disorders in cartilage and skeletal tissues. Fibrodysplasia ossificans progressive, an autosomal genetic disorder characterized by ectopic ossification, is induced by mutant ACVR1. Mechanistic target of rapamycin kinase (mTOR) inhibitors can prevent ectopic ossification induced by ACVR1 mutations. C-type natriuretic peptide is currently the most promising therapy for achondroplasia and related autosomal genetic diseases that manifest severe dwarfism. In these ways, investigation of cartilage and chondrocyte diseases at molecular and cellular levels has enlightened the development of effective therapies. Thus, identification of signaling pathways and transcription factors implicated in these diseases is important.

scholarly journals Epigenetic regulation by the menin pathway

2017 ◽  
Vol 24 (10) ◽  
pp. T147-T159 ◽  
Author(s):  
Zijie Feng ◽  
Jian Ma ◽  
Xianxin Hua
Keyword(s):  
Transcription Factors ◽  
Cell Signaling ◽  
Signaling Pathways ◽  
Gene Transcription ◽  
Epigenetic Regulation ◽  
Posttranslational Modifications ◽  
Genetic Model ◽  
Mirna Biogenesis ◽  
Endocrine Organs

There is a trend of increasing prevalence of neuroendocrine tumors (NETs), and the inherited multiple endocrine neoplasia type 1 (MEN1) syndrome serves as a genetic model to investigate how NETs develop and the underlying mechanisms. Menin, encoded by the MEN1 gene, at least partly acts as a scaffold protein by interacting with multiple partners to regulate cellular homeostasis of various endocrine organs. Menin has multiple functions including regulation of several important signaling pathways by controlling gene transcription. Here, we focus on reviewing the recent progress in elucidating the key biochemical role of menin in epigenetic regulation of gene transcription and cell signaling, as well as posttranslational regulation of menin itself. In particular, we will review the progress in studying structural and functional interactions of menin with various histone modifiers and transcription factors such as MLL, PRMT5, SUV39H1 and other transcription factors including c-Myb and JunD. Moreover, the role of menin in regulating cell signaling pathways such as TGF-beta, Wnt and Hedgehog, as well as miRNA biogenesis and processing will be described. Further, the regulation of the MEN1 gene transcription, posttranslational modifications and stability of menin protein will be reviewed. These various modes of regulation by menin as well as regulation of menin by various biological factors broaden the view regarding how menin controls various biological processes in neuroendocrine organ homeostasis.

scholarly journals Epigenetic Alterations Affecting Transcription Factors and Signaling Pathways in Stromal Cells of Endometriosis

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0170859 ◽  
Author(s):  
Iveta Yotova ◽  
Emily Hsu ◽  
Catherine Do ◽  
Aulona Gaba ◽  
Matthias Sczabolcs ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Signaling Pathways ◽  
Stromal Cells ◽  
Epigenetic Alterations

scholarly journals ASC proneural transcription factors mediate the timely initiation of the neural program during neuroectodermal to neuroblast transition ensuring progeny fidelity

2021 ◽  
Author(s):  
Vasiliki Theodorou ◽  
Aikaterini Stefanaki ◽  
Minas Drakos ◽  
Dafne Triantafyllou ◽  
Christos Delidakis
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Cis Elements ◽  
Enhancer Activity ◽  
Timely Initiation ◽  
Chromatin Dynamics ◽  
Neural Fate ◽  
Neural Specification

Background: ASC/ASCL proneural transcription factors are oncogenic and exhibit impressive reprogramming and pioneer activities. In both Drosophila and mammals, these factors are central in the early specification of the neural fate, where they act in opposition to Notch signalling. However, the role of ASC on the chromatin during CNS neural stem cells birth remains elusive. Results: We investigated the chromatin changes accompanying neural commitment using an integrative genetics and genomics methodology. We found that ASC factors bind equally strongly to two distinct classes of cis-regulatory elements: open regions remodeled earlier during maternal to zygotic transition by Zelda and Zelda-independent, less accessible regions. Both classes cis-elements exhibit enhanced chromatin accessibility during neural specification and correlate with transcriptional regulation of genes involved in many biological processes necessary for neuroblast function. We identified an ASC-Notch regulated TF network that most likely act as the prime regulators of neuroblast function. Using a cohort of ASC target genes, we report that ASC null neuroblasts are defectively specified, remaining initially stalled, lacking expression of many proneural targets and unable to divide. When they eventually start proliferating, they produce compromised progeny. Generation of lacZ reporter lines driven by proneural-bound elements display enhancer activity within neuroblasts and proneural dependency. Therefore, the partial neuroblast identity seen in the absence of ASC genes is driven by other, proneural-independent, cis-elements. Neuroblast impairment and the late differentiation defects of ASC mutants are corrected by ectodermal induction of individual ASC genes but not by individual members of the TF network downstream of ASC. However, in wild type embryos induction of individual members of this network induces CNS hyperplasia, suggesting that they synergize with the activating function of ASC to establish the chromatin dynamics that promote neural specification. Conclusion: ASC factors bind a large number of enhancers to orchestrate the timely activation of the neural chromatin program during neuroectodermal to neuroblast transition. This early chromatin remodeling is crucial for both neuroblast homeostasis as well as future progeny fidelity.

scholarly journals Analysis of genetic networks regulating refractive eye development in collaborative cross progenitor strain mice reveals new genes and pathways underlying human myopia

2019 ◽  
Author(s):  
Tatiana V. Tkatchenko ◽  
Rupal L. Shah ◽  
Takayuki Nagasaki ◽  
Andrei V. Tkatchenko ◽  
◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Refractive Error ◽  
Genetic Background ◽  
Eye Development ◽  
Continuous Distribution ◽  
Genetic Networks ◽  
Visual Environment ◽  
Eye Growth ◽  
Refractive Development ◽  
The Impact

AbstractPopulation studies suggest that genetic factors play an important role in refractive error development; however, the precise role of genetic background and the composition of the signaling pathways underlying refractive eye development remain poorly understood. Here, we analyzed normal refractive development and susceptibility to form-deprivation myopia in the eight progenitor mouse strains of the Collaborative Cross (CC). Genetic background strongly influenced both baseline refractive development and susceptibility to environmentally-induced myopia. Baseline refractive errors ranged from −21.2 diopters (D) in 129S1/svlmj mice to +22.0 D in CAST/EiJ mice and represented a continuous distribution typical of a quantitative genetic trait. The extent of induced form-deprivation myopia ranged from −5.6 D in NZO/HILtJ mice to −20.0 D in CAST/EiJ mice and also followed a continuous distribution. Whole-genome (RNA-seq) gene expression profiling in retinae from CC progenitor strains identified genes whose expression level correlated with either baseline refractive error or susceptibility to myopia. Expression levels of 2,302 genes correlated with the baseline refractive state of the eye, whereas 1,917 genes correlated with susceptibility to induced myopia. Genome-wide gene-based association analysis in the CREAM and UK Biobank human cohorts revealed that 985 of the above genes were associated with refractive error development in humans, including 847 genes which were implicated in the development of human myopia for the first time. Although the gene sets controlling baseline refractive development and those regulating susceptibility to myopia overlapped, these two processes appeared to be controlled by largely distinct sets of genes. Comparison with data for other animal models of myopia revealed that the genes identified in this study comprise a well-defined set of retinal signaling pathways, which are highly conserved across different species. These results provide attractive targets for the development of anti-myopia drugs.Author SummarySeveral lines of evidence suggest that variations in genetic background have a strong impact on a default (baseline) trajectory of eye growth and refractive development. Many studies also highlighted differences in susceptibility of different individuals to environmentally induced changes in refractive eye development, suggesting that genetic background plays an important role in visual regulation of eye growth. However, genes and signaling pathways that control the baseline trajectory of refractive eye development and those that regulate the impact of visual environment on refractive eye development are still poorly understood. Our data suggest that both processes are regulated by elaborate retinal genetic networks. Surprisingly, we found that although genes that control baseline refractive eye development and genes regulating the impact of visual environment on refractive development overlap, there is a large number of genes and pathways which exclusively control either the baseline trajectory of refractive eye development or the impact of visual environment on refractive development. Moreover, we found that many of the genes and pathways, which we found to be associated with either baseline refractive development or susceptibility to environmentally induced myopia in mice, are also associated with refractive error development in the human population and are highly conserved across different species. Identification of genes and pathways that underlie visual regulation of eye growth versus genes and pathways that control default trajectory of refractive eye development sheds light on the basic mechanisms of eye emmetropization and provides previously unexplored possibilities for the development of new treatment options for myopia.

Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm

Development ◽  
2000 ◽  
Vol 127 (4) ◽  
pp. 791-800 ◽  
Author(s):  
M. Kishi ◽  
K. Mizuseki ◽  
N. Sasai ◽  
H. Yamazaki ◽  
K. Shiota ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Glucocorticoid Receptor ◽  
Ligand Binding ◽  
Cell Fate ◽  
Neural Differentiation ◽  
Dominant Negative ◽  
Gastrula Stage ◽  
Blastula Stage ◽  
Sensory Epithelia ◽  
Neural Tissues

From early stages of development, Sox2-class transcription factors (Sox1, Sox2 and Sox3) are expressed in neural tissues and sensory epithelia. In this report, we show that Sox2 function is required for neural differentiation of early Xenopus ectoderm. Microinjection of dominant-negative forms of Sox2 (dnSox2) mRNA inhibits neural differentiation of animal caps caused by attenuation of BMP signals. Expression of dnSox2 in developing embryos suppresses expression of N-CAM and regional neural markers. We have analyzed temporal requirement of Sox2-mediated signaling by using an inducible dnSox2 construct fused to the ligand-binding domain of the glucocorticoid receptor. Attenuation of Sox2 function both from the late blastula stage and from the late gastrula stage onwards causes an inhibition of neural differentiation in animal caps and in whole embryos. Additionally, dnSox2-injected cells that fail to differentiate into neural tissues are not able to adopt epidermal cell fate. These data suggest that Sox2-class genes are essential for early neuroectoderm cells to consolidate their neural identity during secondary steps of neural differentiation.

Identification of transcription factors MYC and C/EBPβ mediated regulatory networks in heart failure based on GEO dataset

2020 ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Hua Cao
Keyword(s):  
Heart Failure ◽  
Transcription Factors ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Regulatory Networks ◽  
Target Genes ◽  
Transcriptional Profiling ◽  
Insulin Signaling Pathway ◽  
Failing Heart

Abstract Background: Heart failure is one of leading cause of death worldwide. However, the transcriptional profiling of heart failure is unclear. Moreover, the signaling pathways and transcription factors involving the heart failure development also are largely unknown. Using published Gene Expression Omnibus (GEO) datasets, in the present study, we aim to comprehensively analyze the differentially expressed genes in failing heart tissues, and identified the critical signaling pathways and transcription factors involving heart failure development. Methods: The transcriptional profiling of heart failure was identified from previously published gene expression datasets deposited in GSE5406, GSE16499 and GSE68316. The enriched signaling pathways and transcription factors were analyzed using DAVID website and gene set enrichment analysis (GSEA) assay. The transcriptional networks were created by Cytoscape. Results: Compared with the normal heart tissues, 90 genes were particularly differentially expressed in failing heart tissues, and those genes were associated with multiple metabolism signaling pathways and insulin signaling pathway. Metabolism and insulin signaling pathway were both inactivated in failing heart tissues. Transcription factors MYC and C/EBPβ were both negatively associated with the expression profiling of failing heart tissues in GSEA assay. Moreover, compared with normal heart tissues, MYC and C/EBPβ were down regulated in failing heart tissues. Furthermore, MYC and C/EBPβ mediated downstream target genes were also decreased in failing heart tissues. MYC and C/EBPβ were positively correlated with each other. At last, we constructed MYC and C/EBPβ mediated regulatory networks in failing heart tissues, and identified the MYC and C/EBPβ target genes which had been reported involving the heart failure developmental progress. Conclusions: Our results suggested that metabolism pathways and insulin signaling pathway, transcription factors MYC and C/EBPβ played critical roles in heart failure developmental progress.

scholarly journals Functions of Jasmonic Acid in Plant Regulation and Response to Abiotic Stress

2020 ◽  
Vol 21 (4) ◽  
pp. 1446 ◽  
Author(s):  
Jia Wang ◽  
Li Song ◽  
Xue Gong ◽  
Jinfan Xu ◽  
Minhui Li
Keyword(s):  
Transcription Factors ◽  
Abiotic Stress ◽  
Jasmonic Acid ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Large Scale ◽  
Higher Plants ◽  
Complex Signal ◽  
Ja Signaling ◽  
Signal Network

Jasmonic acid (JA) is an endogenous growth-regulating substance, initially identified as a stress-related hormone in higher plants. Similarly, the exogenous application of JA also has a regulatory effect on plants. Abiotic stress often causes large-scale plant damage. In this review, we focus on the JA signaling pathways in response to abiotic stresses, including cold, drought, salinity, heavy metals, and light. On the other hand, JA does not play an independent regulatory role, but works in a complex signal network with other phytohormone signaling pathways. In this review, we will discuss transcription factors and genes involved in the regulation of the JA signaling pathway in response to abiotic stress. In this process, the JAZ-MYC module plays a central role in the JA signaling pathway through integration of regulatory transcription factors and related genes. Simultaneously, JA has synergistic and antagonistic effects with abscisic acid (ABA), ethylene (ET), salicylic acid (SA), and other plant hormones in the process of resisting environmental stress.

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