@article{9349, abstract = {The way in which interactions between mechanics and biochemistry lead to the emergence of complex cell and tissue organization is an old question that has recently attracted renewed interest from biologists, physicists, mathematicians and computer scientists. Rapid advances in optical physics, microscopy and computational image analysis have greatly enhanced our ability to observe and quantify spatiotemporal patterns of signalling, force generation, deformation, and flow in living cells and tissues. Powerful new tools for genetic, biophysical and optogenetic manipulation are allowing us to perturb the underlying machinery that generates these patterns in increasingly sophisticated ways. Rapid advances in theory and computing have made it possible to construct predictive models that describe how cell and tissue organization and dynamics emerge from the local coupling of biochemistry and mechanics. Together, these advances have opened up a wealth of new opportunities to explore how mechanochemical patterning shapes organismal development. In this roadmap, we present a series of forward-looking case studies on mechanochemical patterning in development, written by scientists working at the interface between the physical and biological sciences, and covering a wide range of spatial and temporal scales, organisms, and modes of development. Together, these contributions highlight the many ways in which the dynamic coupling of mechanics and biochemistry shapes biological dynamics: from mechanoenzymes that sense force to tune their activity and motor output, to collectives of cells in tissues that flow and redistribute biochemical signals during development.}, author = {Lenne, Pierre François and Munro, Edwin and Heemskerk, Idse and Warmflash, Aryeh and Bocanegra, Laura and Kishi, Kasumi and Kicheva, Anna and Long, Yuchen and Fruleux, Antoine and Boudaoud, Arezki and Saunders, Timothy E. and Caldarelli, Paolo and Michaut, Arthur and Gros, Jerome and Maroudas-Sacks, Yonit and Keren, Kinneret and Hannezo, Edouard B and Gartner, Zev J. and Stormo, Benjamin and Gladfelter, Amy and Rodrigues, Alan and Shyer, Amy and Minc, Nicolas and Maître, Jean Léon and Di Talia, Stefano and Khamaisi, Bassma and Sprinzak, David and Tlili, Sham}, issn = {1478-3975}, journal = {Physical biology}, number = {4}, publisher = {IOP Publishing}, title = {{Roadmap for the multiscale coupling of biochemical and mechanical signals during development}}, doi = {10.1088/1478-3975/abd0db}, volume = {18}, year = {2021}, } @article{8220, abstract = {Understanding to what extent stem cell potential is a cell-intrinsic property or an emergent behavior coming from global tissue dynamics and geometry is a key outstanding question of systems and stem cell biology. Here, we propose a theory of stem cell dynamics as a stochastic competition for access to a spatially localized niche, giving rise to a stochastic conveyor-belt model. Cell divisions produce a steady cellular stream which advects cells away from the niche, while random rearrangements enable cells away from the niche to be favorably repositioned. Importantly, even when assuming that all cells in a tissue are molecularly equivalent, we predict a common (“universal”) functional dependence of the long-term clonal survival probability on distance from the niche, as well as the emergence of a well-defined number of functional stem cells, dependent only on the rate of random movements vs. mitosis-driven advection. We test the predictions of this theory on datasets of pubertal mammary gland tips and embryonic kidney tips, as well as homeostatic intestinal crypts. Importantly, we find good agreement for the predicted functional dependency of the competition as a function of position, and thus functional stem cell number in each organ. This argues for a key role of positional fluctuations in dictating stem cell number and dynamics, and we discuss the applicability of this theory to other settings.}, author = {Corominas-Murtra, Bernat and Scheele, Colinda L.G.J. and Kishi, Kasumi and Ellenbroek, Saskia I.J. and Simons, Benjamin D. and Van Rheenen, Jacco and Hannezo, Edouard B}, issn = {10916490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {29}, pages = {16969--16975}, publisher = {National Academy of Sciences}, title = {{Stem cell lineage survival as a noisy competition for niche access}}, doi = {10.1073/pnas.1921205117}, volume = {117}, year = {2020}, } @article{3, abstract = {SETD5 gene mutations have been identified as a frequent cause of idiopathic intellectual disability. Here we show that Setd5-haploinsufficient mice present developmental defects such as abnormal brain-to-body weight ratios and neural crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are accompanied by abnormal expression of postsynaptic density proteins previously associated with cognition. Our data additionally indicate that Setd5 regulates RNA polymerase II dynamics and gene transcription via its interaction with the Hdac3 and Paf1 complexes, findings potentially explaining the gene expression defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive role of Setd5 in a biological pathway found to be disrupted in humans with intellectual disability and autism spectrum disorder.}, author = {Deliu, Elena and Arecco, Niccoló and Morandell, Jasmin and Dotter, Christoph and Contreras, Ximena and Girardot, Charles and Käsper, Eva and Kozlova, Alena and Kishi, Kasumi and Chiaradia, Ilaria and Noh, Kyung and Novarino, Gaia}, journal = {Nature Neuroscience}, number = {12}, pages = {1717 -- 1727}, publisher = {Nature Publishing Group}, title = {{Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition}}, doi = {10.1038/s41593-018-0266-2}, volume = {21}, year = {2018}, }