A closed feedback between tissue phase transitions and morphogen gradients drives patterning dynamics in the zebrafish embryo
How tissues are formed is a fundamental question in developmental biology. During morphogenesis, tissue shaping is brought about by mechanochemical circuits, where biochemical signals instructing cell fate decisions are coordinated with mechanical signals regulating shape changes. Although extensive...
Salvato in:
| Autore principale: | |
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| Natura: | Book/Monograph Tesi |
| Lingua: | inglese |
| Pubblicazione: |
Heidelberg
27 Mrz. 2026
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| DOI: | 10.11588/heidok.00037144 |
| Soggetti: | |
| Accesso online: | Resolving-System, kostenfrei: https://nbn-resolving.de/urn:nbn:de:bsz:16-heidok-371444 Resolving-System, kostenfrei: https://doi.org/10.11588/heidok.00037144 Verlag, kostenfrei, Volltext: http://www.ub.uni-heidelberg.de/archiv/37144 
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| Note sull'autore: | presented by M.Sc.Camilla Autorino ; referees: Prof. Dr. Lazaro Centanin [und ein weiterer Gutachter] |
| Riassunto: | How tissues are formed is a fundamental question in developmental biology. During morphogenesis, tissue shaping is brought about by mechanochemical circuits, where biochemical signals instructing cell fate decisions are coordinated with mechanical signals regulating shape changes. Although extensive work has been performed in the past decades on the mechanisms driving cell fate decisions, leading to the long-established view that cells read local variations in morphogen concentrations, the idea that decisionmaking is also orchestrated by global properties arising at the supracellular, or collective-level, like tissue geometry or rigidity, has only begun to be explored. For my doctoral thesis, I elucidated the mechanisms linking morphogen signalling and tissue-scale rigidity in the first cell fate decision in zebrafish embryogenesis, the mesendodermal patterning. Using quantitative imaging analysis and rigidity percolation theory I found that mesendoderm specification, occurs simultaneously with an abrupt transition in its tissue material properties, tissue rigidification. To ask if there is an interplay between the underlying morphogens instructing mesendoderm specification and tissue material properties, I took an interdisciplinary approach, combining genetics, optogenetics with theoretical predictions. I showed that the length scales and time scales of the Nodal morphogen dispersal and activity are tuned by the rigidity transition. Nodal, while inducing mesendoderm fate specification, also increases cell-cell adhesion strength via regulating the expression of planar cell polarity genes. As adhesion strength passes its critical point, at which global tissue rigidity arises, tissue porosity sharply drops. I found that these abrupt Nodal-dependent changes in tissue architecture limit Nodal diffusivity, concentrating the ligands close to the source. As a result, Nodal signalling increases closer to the source, which leads to the prompt expression of its antagonist Lefty, to terminate Nodal activity via biochemical inhibition. Overall, I propose a closed feedback loop mechanism where emergent macroscopic properties regulate morphogen gradient formation, to ensure patterning precision in space and time. |
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| Descrizione fisica: | Online Resource |
| DOI: | 10.11588/heidok.00037144 |