<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "The link between glycolysis and signaling during mouse embryo segmentation"^^ . "New phenotypes can arise in organisms as a response to changing environments. Changes\r\nin environmental conditions, such as temperature fluctuations, pressure changes, or nutrient\r\navailability, are translated into cellular processes, thus giving rise to new phenotypes without\r\naffecting the genotype. Metabolism can be a translator of such environmental changes. It is\r\nbeing recognized more and more how metabolism can not only have a bioenergetic role but\r\nalso affect signaling, gene expression, epigenetics, post-translational modifications, etc.\r\nI have conducted this work in mouse embryos, where Hidenobu Miyazawa has observed\r\na phenotype in developmental timing as a result of changes in glycolytic flux. Previous\r\ndata shows that increasing glycolytic flux in the presomitic mesoderm (PSM) slows down\r\nthe tempo of the segmentation clock (a molecular clock that controls the patterning of the\r\nPSM). Because of these previous findings, I was interested in investigating the link between\r\nglycolysis and signaling in the PSM.\r\nI addressed the questions in the first part of this work by applying a microfluidics-based\r\nentrainment approach. Entrainment is a fundamental property of oscillating systems, which\r\noccurs when an oscillator adjusts its phase and its period to an external periodic pertur-\r\nbation, thus getting entrained to it. It has been shown before that glucose can entrain the\r\nsegmentation clock, so first, I expanded the approach of glycolytic entrainment and tested\r\nwhich glycolytic metabolites can entrain the segmentation clock. The segmentation clock\r\nconsists of an intricate network of different signaling pathways, such as Notch, Wnt, and\r\nFGF. I attempted entrainment of Notch oscillations (which are the core oscillatory compo-\r\nnent of the segmentation clock) with fructose-6-phosphate (F6P), fructose-1,6-bisphosphate\r\n(FBP), and pyruvate. I quantified the efficiency of entrainment by F6P, FBP and pyruvate\r\nby using the entrainment phase and in-phase synchrony as readouts. I identified FBP as a\r\nZeitgeber (an external cue that synchronizes an organism’s intrinsic clock), which entrained \r\nboth Notch and Wnt oscillations based on the predefined criteria. I showed that FBP pulses\r\nchange the phase of entrainment when pulses are applied at different periods (detunings).\r\nI saw a difference in timing to entrainment between Wnt and Notch during entrainment\r\nwith FBP pulses, hinting at a differential relationship between FBP and these two signaling\r\npathways. The segmentation clock did not get entrained by pulses of pyruvate. Therefore,\r\nI suggest that the part of glycolysis that is linked to signaling might be confined between\r\nFBP and pyruvate (excluding pyruvate).\r\nFurthermore, I investigated whether glycolysis has a signaling role in the segmentation\r\nclock and how glycolysis is functionally linked to signaling during mouse embryo segmen-\r\ntation. I tried to disentangle the functional link of FBP to signaling by entraining with\r\ncombination pulses of FBP and signaling perturbations of Wnt and Notch. By using pre-\r\ndictions from theory of dynamical systems, I showed that FBP functions as a signal in\r\nentraining the segmentation clock, hinting at a role of FBP in the PSM that goes beyond\r\nits bioenergetic function. I made some predictions about the functional link between FBP\r\nand signaling based on the resulting phases of entrainment after applying combined pulses\r\nof FBP and signaling perturbations.\r\nIn the second part of this work, I explored the presence of glycolytic oscillations in the PSM\r\nby using Ca2+ oscillations as indirect evidence. I discovered that there are Ca2+ oscillations\r\npresent in the PSM, which are induced by glucose and F6P supplementation in the medium,\r\nwhereas they are depleted by FBP and pyruvate supplementation. Thus, I gathered some\r\nfirst evidence, which suggests that it might be worth it to develop FBP sensors in mice in\r\norder to consolidate the presence of glycolytic rhythms in the PSM."^^ . "2024" . . . . . . . "Jona"^^ . "Rada"^^ . "Jona Rada"^^ . . . . . . "The link between glycolysis and signaling during mouse embryo segmentation (PDF)"^^ . . . "Thesis_Rada_Final_first_person.pdf"^^ . . . "The link between glycolysis and signaling during mouse embryo segmentation (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "The link between glycolysis and signaling during mouse embryo segmentation (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "The link between glycolysis and signaling during mouse embryo segmentation (Other)"^^ . . . . . . "preview.jpg"^^ . . . "The link between glycolysis and signaling during mouse embryo segmentation (Other)"^^ . . . . . . "medium.jpg"^^ . . . "The link between glycolysis and signaling during mouse embryo segmentation (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #35470 \n\nThe link between glycolysis and signaling during mouse embryo segmentation\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .