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Neuroendocrine Interactions in the Control of Glucose- and Energy Homeostasis
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
The WNT pathway was first described in 1976 when it was reported that Drosophila Melanogaster has a wingless phenotype when this pathway is mutated (92). In 1982, the same signalling cascade was found to promote tumour formation in mice, and therefore given the term ‘integration-1 (int1)’ (93). ‘Wingless’ and ‘int1’ were later combined, and thus, the WNT pathway was coined. The WNT signalling pathway is evolutionarily highly conserved and is classically known for its role in embryogenesis and tumorigenesis (94). Its ligands (WNTs) are involved in three different pathways: the WNT/β-catenin pathway (also known as the canonical WNT pathway), the planar cell polarity pathway, and the WNT/Ca2+ pathway. The canonical WNT pathway is activated when a WNT ligand binds to the frizzled (Fzd) receptor, which subsequently forms a complex with the co-receptor lipoprotein related protein (LRP) 5/6. This causes dishevelled (Dvl) to phosphorylate LRP, which then inactivates GSK3β. Next, GSK3β inactivation decreases phosphorylation of the transcriptional co-activator β-catenin. Stabilized β-catenin then enters the nucleus where it associates with transcription factors of the lymphoid enhancer factor (LEF)/T cell factor (TCF) family, to ultimately regulate the transcription of downstream target genes such as cyclin D1 and axin 2 (95).
Notch signaling in spermatogenesis and male (in)fertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Mahitha Sahadevan, Pradeep G. Kumar
In this chapter, we focus on the role of notch signaling in regulating spermatogenesis, with special emphasis on C. elegans, Drosophila melanogaster and Mus musculus. This chapter is divided into three sections—the first section deals with the general concepts regarding the structure and function of the notch and the modulation of notch signaling. The second section focuses on how notch signaling regulates spermatogenesis and the cross talk between notch signaling and other pathways. The third section deals with how the dysfunction of notch signaling acts as a leading cause of male infertility. Finally, the future perspectives in this field are discussed.
Notes on Genetic and Radiation Control of Senescence
Published in Nate F. Cardarelli, The Thymus in Health and Senescence, 2019
Studies involving the PER locus in Drosophila melanogaster DNA have been instructive. This 7.1 kb hind III fragment is responsible for behavioral rhythms.287 PER mutants show abnormal clocking.288 While the normal fruitfly circadian clock is 24 h, PER1 mutants have a 29-h clock, PER8 a 19-h clock, and PER0 are arrhythmic. A gene from PER normal transferred into PERo initiates normal rhythmicity. Homologous PER sequences have been found in the DNA of the chicken, mouse, and man.289
Evaluating Water bitter leaf (Struchium sparganophora) and Scent Leaf (Ocimum gratissimum) extracts as sources of nutraceuticals against manganese-induced toxicity in fruit fly model
Published in Drug and Chemical Toxicology, 2023
Adedayo Oluwaseun Ademiluyi, Opeyemi Babatunde Ogunsuyi, Josephine Oluwaseun Akinduro, Olayemi Philemon Aro, Ganiyu Oboh
The fruit fly (Drosophila melanogaster), is one of the most studied eukaryotic organisms and has made fundamental contributions to different areas of biology. It has also gained appreciation as a useful animal model of human diseases. Comparative genomic studies estimate that up to 75% of the human genes implicated in diseases are expressed in Drosophila (Ugur et al. 2016). The similarity between human and Drosophila genomes is not limited to only genetic, but also numerous conserved biological mechanisms. The Drosophila genome is smaller in size and has a smaller number of genes compared to the human genome, which facilitates genetic studies. The fruit fly Drosophila melanogaster has proven to be a powerful platform with plenty of amenable genetic techniques to investigate the mechanism of human neurodegenerative diseases (Bilen and Bonini 2005).
Potential signaling pathway through which Notch regulates oxidative damage and apoptosis in renal tubular epithelial cells induced by high glucose
Published in Journal of Receptors and Signal Transduction, 2021
Ziyang Jing, Langtao Hu, Yan Su, Gangqiang Ying, Chunyang Ma, Jiali Wei
The Notch gene was first recognized in Drosophila by Morgan, who named the gene for the marginal notch (Notch) of the wings Drosophila melanogaster, resulting in impaired function. The Notch protein family, a transmembrane receptor protein family, is widespread in vertebrates and invertebrates and highly conserved, can mediate interactions between cells, and plays an important role in determining cell fate. Moreover, Notch can be reactivated in disease states and can participate in the processes of apoptosis, regeneration, and tubule mesenchymal transition and can affect the occurrence and development of many kinds of kidney diseases through cross talk with other signaling pathways (across-talk). Upon the binding of the Notch signaling pathway ligand to the receptor, the Notch receptor undergoes conformational changes, mediating the release of the Notch intracellular domain (NICD) by gamma secretase. NICD is the activated form of Notch, which enters the nucleus to activate the downstream regulatory genes Hes and Hey and induce the differentiation of cells [10].
Marla Sokolowski: and now for someone completely different
Published in Journal of Neurogenetics, 2021
H. Sofia Pereira, Karen D. Williams, J. Steven de Belle
Drosophila melanogaster is the ideal model system for hands-on genetics instruction, easily permitting young researchers to initiate research in a laboratory setting. Undergraduates from Marla’s courses were frequently encouraged to visit the lab and test-drive their basic fly pushing skills. During the ‘York’ years, students sustained with beer money and bus fare stipends were often introduced to research with summer fly projects. Since the Drosophila larval pathlength assay required many hands working together, trainees also had the opportunity to ‘get their fingers wet’ in collaborative research. The Sokolowski lab always incentivized inclusivity, where the scientific process was knitted together by each one’s experiences in conducting research as well as developing critical thinking and communication skills. As in many well-oiled scientific machines, this stimulating social environment enabled by Marla was creative, productive, and great fun. Unfortunately, and for the sake of simplicity, many legendary stories have been necessarily omitted from this tribute to our former leader.