Patterning the dorsal longitudinal flight muscles (DLM) of Drosophila: insights from the ablation of larval scaffolds

Development ◽  
1996 ◽  
Vol 122 (12) ◽  
pp. 3755-3763 ◽  
Author(s):  
J.J. Fernandes ◽  
H. Keshishian
Keyword(s):  
Transcription Factor ◽  
De Novo ◽  
Muscle Fibers ◽  
Myoblast Fusion ◽  
The Other ◽  
Correct Number ◽  
Larval Muscle ◽  
Actin Isoform ◽  
Flight Muscles

The six Dorsal Longitudinal flight Muscles (DLMs) of Drosophila develop from three larval muscles that persist into metamorphosis and serve as scaffolds for the formation of the adult fibers. We have examined the effect of muscle scaffold ablation on the development of DLMs during metamorphosis. Using markers that are specific to muscle and myoblasts we show that in response to the ablation, myoblasts which would normally fuse with the larval muscle, fuse with each other instead, to generate the adult fibers in the appropriate regions of the thorax. The development of these de novo DLMs is delayed and is reflected in the delayed expression of erect wing, a transcription factor thought to control differentiation events associated with myoblast fusion. The newly arising muscles express the appropriate adult-specific Actin isoform (88F), indicating that they have the correct muscle identity. However, there are frequent errors in the number of muscle fibers generated. Ablation of the larval scaffolds for the DLMs has revealed an underlying potential of the DLM myoblasts to initiate de novo myogenesis in a manner that resembles the mode of formation of the Dorso-Ventral Muscles, DVMs, which are the other group of indirect flight muscles. Therefore, it appears that the use of larval scaffolds is a superimposition on a commonly used mechanism of myogenesis in Drosophila. Our results show that the role of the persistent larval muscles in muscle patterning involves the partitioning of DLM myoblasts, and in doing so, they regulate formation of the correct number of DLM fibers.

scholarly journals BRN2 is a non-canonical melanoma tumor-suppressor

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michael Hamm ◽  
Pierre Sohier ◽  
Valérie Petit ◽  
Jérémy H. Raymond ◽  
Véronique Delmas ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Tumor Suppressor ◽  
The Other ◽  
Pi3k Signaling ◽  
Melanoma Tumor ◽  
Temporal Regulation ◽  
Metastatic Colonization ◽  
Pou Domain

AbstractWhile the major drivers of melanoma initiation, including activation of NRAS/BRAF and loss of PTEN or CDKN2A, have been identified, the role of key transcription factors that impose altered transcriptional states in response to deregulated signaling is not well understood. The POU domain transcription factor BRN2 is a key regulator of melanoma invasion, yet its role in melanoma initiation remains unknown. Here, in a BrafV600EPtenF/+ context, we show that BRN2 haplo-insufficiency promotes melanoma initiation and metastasis. However, metastatic colonization is less efficient in the absence of Brn2. Mechanistically, BRN2 directly induces PTEN expression and in consequence represses PI3K signaling. Moreover, MITF, a BRN2 target, represses PTEN transcription. Collectively, our results suggest that on a PTEN heterozygous background somatic deletion of one BRN2 allele and temporal regulation of the other allele elicits melanoma initiation and progression.

scholarly journals Role of DBP in the Circadian Oscillatory Mechanism

2000 ◽  
Vol 20 (13) ◽  
pp. 4773-4781 ◽  
Author(s):  
Shun Yamaguchi ◽  
Shigeru Mitsui ◽  
Lily Yan ◽  
Kazuhiro Yagita ◽  
Shigeru Miyake ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Leucine Zipper ◽  
The Other ◽  
Suprachiasmatic Nuclei ◽  
Transcription Factor Family ◽  
Transcript Levels ◽  
Oscillatory Mechanism ◽  
Central Clock ◽  
E Boxes

ABSTRACT Transcript levels of DBP, a member of the PAR leucine zipper transcription factor family, exhibit a robust rhythm in suprachiasmatic nuclei, the mammalian circadian center. Here we report that DBP is able to activate the promoter of a putative clock oscillating gene,mPer1, by directly binding to the mPer1promoter. The mPer1 promoter is cooperatively activated by DBP and CLOCK-BMAL1. On the other hand, dbp transcription is activated by CLOCK-BMAL1 through E-boxes and inhibited by the mPER and mCRY proteins, as is the case for mPer1. Thus, a clock-controlled dbp gene may play an important role in central clock oscillation.

scholarly journals A New Entity of Acute Myeloid Leukemia Driven By Epigenetic and Somatic Dis-Regulation of Uncx, a Novel Homeobox Transcription Factor Gene

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1356-1356
Author(s):  
Giulia Daniele ◽  
Clelia Tiziana Storlazzi ◽  
Cristina Papayannidis ◽  
Ilaria Iacobucci ◽  
Angelo Lonoce ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Transcription Factor ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Ectopic Expression ◽  
Response To Therapy ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Abstract We describe a new AML entity, occurring in 30% of de novo acute myeloid leukemia, due to structural and epigenetic deregulation of the UNCX homeobox (HB) gene. By molecular approaches, we identified a M5 AML patient with a t(7;10)(p22;p14) translocation as the sole cytogenetic anomaly and showing ectopic expression of UNCX (7p22.3), which encode for a transcription factor involved in somitogenesis and neurogenesis. Since UNCX was never reported in association with cancer but only with common myeloid cell proliferation and regulation of cell differentiation, we decided to investigate its contribution to leukemogenesis. We observed UNCX ectopic expression in 32.3% (20/62) and in 8% (6/75) of acute myeloid leukemia (AML) patients and cell lines, respectively. Notably, retroviral-mediated UNCX transfer in CD34+ HSCs induced a slow-down in their proliferation and differentiation and transduced cells showed a lower growth rate but a higher percentage of CD34+ stem cells in liquid culture than controls. Additionally, UNCX infected cells displayed a decrease of MAP2K1 proliferation marker but increase of KLF4, HOXA10, and CCNA1, associated with impaired differentiation and pluripotency. Similarly, UNCX-positive patients revealed alteration of gene pathways involved in proliferation, cell cycle control and hematopoiesis. Since HB genes encode for transcription factors showing a crucial role in normal hematopoiesis and in leukemogenesis, we focused our attention on the role of altered UNCX expression level. Of note, its murine ortholog, (Uncx) was previously described as embedded within a low-methylated regions (≤ 10%) called "canyon" and dysregulated in murine hematopoietic stem cells (HSCs) as a consequence of altered methylation at canyons edges (borders) due to Dnmt3a inactivation. In our hands, UNCX activation was accompanied by methylation changes at both its canyon borders, clearly indicating an epigenetic regulation of this gene, although not induced by DNMT3A mutations. Clinical parameters and correlation with response to therapy will be presented. Taken together, our results indicate that more than 30% of de novo AML have a novel entity with a putative leukemogenic role of UNCX, whose activation may be ascribed to epigenetic regulators. Acknowledgments: MG, CP, GS, and AP(2) and this work was supported by ELN, AIL, AIRC, progetto Regione-Università 2010-12 (L. Bolondi), Fondazione del Monte di Bologna e Ravenna, FP7 NGS-PTL project. CTS, GD and AL are supported by Associazione Italiana Ricerca sul Cancro (AIRC) funding. Disclosures Nadarajah: MLL Munich Leukemia Laboratory: Employment. Martinelli:MSD: Consultancy; Novartis: Consultancy, Speakers Bureau; Ariad: Consultancy; BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy; AMGEN: Consultancy; ROCHE: Consultancy.

scholarly journals News about the Role of the Transcription Factor REST in Neurons: From Physiology to Pathology

2019 ◽  
Vol 21 (1) ◽  
pp. 235 ◽  
Author(s):  
Jose M. Garcia-Manteiga ◽  
Rosalba D’Alessandro ◽  
Jacopo Meldolesi
Keyword(s):  
Transcription Factor ◽  
Neurodegenerative Diseases ◽  
The Other ◽  
Brain Diseases ◽  
Strong Decrease ◽  
Future Developments ◽  
The Past

RE-1 silencing transcription factor (REST) (known also as NRSF) is a well-known transcription repressor whose strong decrease induces the distinction of neurons with respect to the other cells. Such distinction depends on the marked increased/decreased expression of specific genes, accompanied by parallel changes of the corresponding proteins. Many properties of REST had been identified in the past. Here we report those identified during the last 5 years. Among physiological discoveries are hundreds of genes governed directly/indirectly by REST, the mechanisms of its neuron/fibroblast conversions, and the cooperations with numerous distinct factors induced at the epigenetic level and essential for REST specific functions. New effects induced in neurons during brain diseases depend on the localization of REST, in the nucleus, where functions and toxicity occur, and in the cytoplasm. The effects of REST, including cell aggression or protection, are variable in neurodegenerative diseases in view of the distinct mechanisms of their pathology. Moreover, cooperations are among the mechanisms that govern the severity of brain cancers, glioblastomas, and medulloblastomas. Interestingly, the role in cancers is relevant also for therapeutic perspectives affecting the REST cooperations. In conclusion, part of the new REST knowledge in physiology and pathology appears promising for future developments in research and brain diseases.

A novel SLC2A1 mutation linking hemiplegic migraine with alternating hemiplegia of childhood

Cephalalgia ◽  
2014 ◽  
Vol 35 (1) ◽  
pp. 10-15 ◽  
Author(s):  
Claudia M Weller ◽  
Wilhelmina G Leen ◽  
Brian GR Neville ◽  
John S Duncan ◽  
Boukje de Vries ◽  
...  
Keyword(s):  
De Novo ◽  
The Other ◽  
Brain Disorders ◽  
Complex Phenotype ◽  
Hemiplegic Migraine ◽  
Alternating Hemiplegia Of Childhood ◽  
Genetic Overlap ◽  
Slc2a1 Gene ◽  
Small Set

Background Hemiplegic migraine (HM) and alternating hemiplegia of childhood (AHC) are rare episodic neurological brain disorders with partial clinical and genetic overlap. Recently, ATP1A3 mutations were shown to account for the majority of AHC patients. In addition, a mutation in the SLC2A1 gene was reported in a patient with atypical AHC. We therefore investigated whether mutations in these genes may also be involved in HM. Furthermore, we studied the role of SLC2A1 mutations in a small set of AHC patients without ATP1A3 mutations. Methods We screened 42 HM patients (21 familial and 21 sporadic patients) for ATP1A3 and SLC2A1 mutations. In addition, four typical AHC patients and one atypical patient with overlapping symptoms of both disorders were screened for SLC2A1 mutations. Results A pathogenic de novo SLC2A1 mutation (p.Gly18Arg) was found in the atypical patient with overlapping symptoms of AHC and hemiplegic migraine. No mutations were found in the HM and the other AHC patients. Conclusion Screening for a mutation in the SLC2A1 gene should be considered in patients with a complex phenotype with overlapping symptoms of hemiplegic migraine and AHC.

scholarly journals Strategies for acquiring the phospholipid metabolite inositol in pathogenic bacteria, fungi and protozoa: making it and taking it

Microbiology ◽  
2009 ◽  
Vol 155 (5) ◽  
pp. 1386-1396 ◽  
Author(s):  
Todd B. Reynolds
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Candida Albicans ◽  
Trypanosoma Brucei ◽  
Pathogenic Bacteria ◽  
De Novo ◽  
The Other ◽  
Inositol Monophosphatase ◽  
Essential Nutrient ◽  
Phosphate Synthase

myo-Inositol (inositol) is an essential nutrient that is used for building phosphatidylinositol and its derivatives in eukaryotes and even in some eubacteria such as the mycobacteria. As a consequence, fungal, protozoan and mycobacterial pathogens must be able to acquire inositol in order to proliferate and cause infection in their hosts. There are two primary mechanisms for acquiring inositol. One is to synthesize inositol from glucose 6-phosphate using two sequentially acting enzymes: inositol-3-phosphate synthase (Ino1p) converts glucose 6-phosphate to inositol 3-phosphate, and then inositol monophosphatase (IMPase) dephosphorylates inositol 3-phosphate to generate inositol. The other mechanism is to import inositol from the environment via inositol transporters. Inositol is readily abundant in the bloodstream of mammalian hosts, providing a source from which many pathogens could potentially import inositol. However, despite this abundance of inositol in the host, some pathogens such as the bacterium Mycobacterium tuberculosis and the protist parasite Trypanosoma brucei must be able to make inositol de novo in order to cause disease (M. tuberculosis) or even grow (T. brucei). Other pathogens such as the fungus Candida albicans are equally adept at causing disease by importing inositol or by making it de novo. The role of inositol acquisition in the biology and pathogenesis of the parasite Leishmania and the fungus Cryptococcus are being explored as well. The specific strategies used by these pathogens to acquire inositol while in the host are discussed in relation to each pathogen's unique metabolic requirements.

scholarly journals Importance of Trehalose Biosynthesis for Sinorhizobium meliloti Osmotolerance and Nodulation of Alfalfa Roots

2009 ◽  
Vol 191 (24) ◽  
pp. 7490-7499 ◽  
Author(s):  
Ana Domínguez-Ferreras ◽  
María J. Soto ◽  
Rebeca Pérez-Arnedo ◽  
José Olivares ◽  
Juan Sanjuán
Keyword(s):  
Sinorhizobium Meliloti ◽  
De Novo ◽  
The Other ◽  
Biosynthesis Pathway ◽  
De Novo Biosynthesis ◽  
Common Response ◽  
Trehalose Biosynthesis ◽  
Trehalose Synthesis ◽  
Trehalose Accumulation

ABSTRACT The disaccharide trehalose is a well-known osmoprotectant, and trehalose accumulation through de novo biosynthesis is a common response of bacteria to abiotic stress. In this study, we have investigated the role of endogenous trehalose synthesis in the osmotolerance of Sinorhizobium meliloti. Genes coding for three possible trehalose synthesis pathways are present in the genome of S. meliloti 1021: OtsA, TreYZ, and TreS. Among these, OtsA has a major role in trehalose accumulation under all of the conditions tested and is the main system involved in osmoadaptation. Nevertheless, the other two systems are also important for growth in hyperosmotic medium. Genes for the three pathways are transcriptionally responsive to osmotic stress. The presence of at least one functional trehalose biosynthesis pathway is required for optimal competitiveness of S. meliloti to nodulate alfalfa roots.

scholarly journals Filopodia powered by class X myosin promote fusion of mammalian myoblasts

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
David W Hammers ◽  
Cora C Hart ◽  
Michael K Matheny ◽  
Ernest G Heimsath ◽  
Young il Lee ◽  
...  
Keyword(s):  
Fusion Proteins ◽  
Muscle Injury ◽  
Muscle Fibers ◽  
Myoblast Fusion ◽  
Mammalian Muscle ◽  
Muscle Formation ◽  
Resident Stem Cells

Skeletal muscle fibers are multinucleated cellular giants formed by the fusion of mononuclear myoblasts. Several molecules involved in myoblast fusion have been discovered, and finger-like projections coincident with myoblast fusion have also been implicated in the fusion process. The role of these cellular projections in muscle cell fusion was investigated herein. We demonstrate that these projections are filopodia generated by class X myosin (Myo10), an unconventional myosin motor protein specialized for filopodia. We further show that Myo10 is highly expressed by differentiating myoblasts, and Myo10 ablation inhibits both filopodia formation and myoblast fusion in vitro. In vivo, Myo10 labels regenerating muscle fibers associated with Duchenne muscular dystrophy and acute muscle injury. In mice, conditional loss of Myo10 from muscle-resident stem cells, known as satellite cells, severely impairs postnatal muscle regeneration. Furthermore, the muscle fusion proteins Myomaker and Myomixer are detected in myoblast filopodia. These data demonstrate that Myo10-driven filopodia facilitate multi-nucleated mammalian muscle formation.

scholarly journals Genetic Analysis of Myc and Telomerase Interactions In Vivo

2006 ◽  
Vol 26 (16) ◽  
pp. 6130-6138 ◽  
Author(s):  
Ignacio Flores ◽  
Gerard Evan ◽  
María A. Blasco
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
The Other ◽  
Induced Response ◽  
Direct Role ◽  
Myc Gene ◽  
Late Generation ◽  
Transcriptional Target

ABSTRACT Myc is a transcription factor with pleiotropic effects on tumorigenesis which are likely to be mediated by its target genes. A known Myc transcriptional target is the catalytic subunit of telomerase, Tert. However, the contribution of Tert activation to Myc-induced tumorigenesis in vivo remains unknown. In this study, we addressed the role of telomerase in Myc-induced skin papillomatosis by using compound mice with a switchable Myc gene, Inv-MycERTAM mice, in combination with either telomerase deficiency (Terc−/−) or telomerase overexpression (K5-mTert) in the skin. We first demonstrated that Myc activates telomerase in the skin. With Inv-MycERTAM × Terc−/− mice, we further showed that this telomerase activation is partially required to elicit a full hyperplastic Myc-induced response. The presence of critically short telomeres in late-generation Inv-MycERTAM × Terc−/− mice further reduced the skin lesion induced by Myc. On the other hand, telomerase overexpression in the skin of K5-mTert mice augments Myc-induced hyperplasia in the absence of changes in telomere length, suggesting a direct role of telomerase in the Myc protumorigenic response. Taken together, these results highlight telomerase as a mediator of Myc-induced papillomatosis and suggest telomerase as a putative therapeutic target for Myc-dependent lesions.

scholarly journals A Novel cis Element Achieves the Same Solution as an Ancestral cis Element During Thiamine Starvation in Candida glabrata

2019 ◽  
Vol 10 (1) ◽  
pp. 321-331 ◽  
Author(s):  
Christine L. Iosue ◽  
Anthony P. Gulotta ◽  
Kathleen B. Selhorst ◽  
Alison C. Mody ◽  
Kristin M. Barbour ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Site ◽  
Candida Glabrata ◽  
Regulatory Networks ◽  
The Other ◽  
Factor Binding Site ◽  
Cis Element ◽  
Element Evolution

Regulatory networks often converge on very similar cis sequences to drive transcriptional programs due to constraints on what transcription factors are present. To determine the role of constraint loss on cis element evolution, we examined the recent appearance of a thiamine starvation regulated promoter in Candida glabrata. This species lacks the ancestral transcription factor Thi2, but still has the transcription factor Pdc2, which regulates thiamine starvation genes, allowing us to determine the effect of constraint change on a new promoter. We identified two different cis elements in C. glabrata - one present in the evolutionarily recent gene called CgPMU3, and the other element present in the other thiamine (THI) regulated genes. Reciprocal swaps of the cis elements and incorporation of the S. cerevisiaeThi2 transcription factor-binding site into these promoters demonstrate that the two elements are functionally different from one another. Thus, this loss of an imposed constraint on promoter function has generated a novel cis sequence, suggesting that loss of trans constraints can generate a non-convergent pathway with the same output.

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