<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "The regulation and scaling of developmental tempo across mammalian species"^^ . "The speed of embryonic development varies considerably across mammalian species. These differences\r\nin the tempo or duration of developmental processes are known to influence the final size and shape of\r\norganisms, serving as an important mechanism of evolutionary change. This thesis aims to understand\r\nhow different mammals, despite using seemingly indistinguishable molecular toolkits, exhibit speciesspecific\r\ndevelopmental rates. To this end, I have focused on investigating the timing of the vertebrate\r\nbody axis segmentation.\r\nThe rate at which body segments form is controlled by the segmentation clock, the oscillatory gene\r\nexpression found in the pre-somitic mesoderm (PSM) cells. The period of the segmentation clock\r\noscillations differs greatly across vertebrates. However, investigating these temporal differences has\r\nproved challenging due to the difficulties in obtaining and quantitatively comparing embryos from\r\ndifferent animal species. To overcome these challenges, I have used pluripotent stem cells (PSCs) from\r\nvarious mammals, a \"stem cell zoo\", to develop in vitro models of the segmentation clock. By\r\ndifferentiating PSCs into PSM cells, I have been able to study the developmental tempo of six\r\nmammalian species under similar experimental conditions. These species include humans, mice,\r\nrabbits, cattle, rhinoceros, and marmosets, which span a wide range of body sizes and morphologies.\r\nQuantification of the segmentation clock oscillations revealed that their period scaled with the\r\nembryogenesis length rather than animal body weight. The biochemical kinetics of the core clock gene\r\nHES7 showed clear scaling with the species-specific segmentation clock period. However, cellular\r\nmetabolic rates did not exhibit a similar correlation. Instead, genes involved in biochemical reactions\r\ndisplayed expression patterns that scaled with the segmentation clock period, providing evidence of the\r\ntranscriptional regulation of developmental tempo. To further explore this transcriptomic signature, I\r\nestablished a pipeline for screening genetic modifications affecting the segmentation clock period in\r\nhuman cells. By combining novel fluorescent reporters of biochemical kinetics with gene expression\r\nperturbations, I isolated human cell clones with accelerated or decelerated segmentation clock periods.\r\nCharacterization of these clones revealed specific genes capable of modulating the segmentation clock\r\nperiod.\r\nOverall, the stem cell zoo has uncovered general scaling laws governing developmental tempo at the\r\ncellular level. This research provides further insights into the mechanisms used by evolution to generate\r\nmorphological diversity across species."^^ . "2024" . . . . . . . "Jorge"^^ . "Lázaro Farré"^^ . "Jorge Lázaro Farré"^^ . . . . . . "The regulation and scaling of developmental tempo across mammalian species (PDF)"^^ . . . "Thesis_JorgeLazaro.pdf"^^ . . . "The regulation and scaling of developmental tempo across mammalian species (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "The regulation and scaling of developmental tempo across mammalian species (Other)"^^ . . . . . . "preview.jpg"^^ . . . "The regulation and scaling of developmental tempo across mammalian species (Other)"^^ . . . . . . "medium.jpg"^^ . . . "The regulation and scaling of developmental tempo across mammalian species (Other)"^^ . . . . . . "small.jpg"^^ . . . "The regulation and scaling of developmental tempo across mammalian species (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #35506 \n\nThe regulation and scaling of developmental tempo across mammalian species\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .