@article{5787, abstract = {Branching morphogenesis remains a subject of abiding interest. Although much is known about the gene regulatory programs and signaling pathways that operate at the cellular scale, it has remained unclear how the macroscopic features of branched organs, including their size, network topology and spatial patterning, are encoded. Lately, it has been proposed that, these features can be explained quantitatively in several organs within a single unifying framework. Based on large- scale organ recon - structions and cell lineage tracing, it has been argued that morphogenesis follows from the collective dynamics of sublineage- restricted self- renewing progenitor cells, localized at ductal tips, that act cooperatively to drive a serial process of ductal elon - gation and stochastic tip bifurcation. By correlating differentiation or cell cycle exit with proximity to maturing ducts, this dynamic results in the specification of a com- plex network of defined density and statistical organization. These results suggest that, for several mammalian tissues, branched epithelial structures develop as a self- organized process, reliant upon a strikingly simple, but generic, set of local rules, without recourse to a rigid and deterministic sequence of genetically programmed events. Here, we review the basis of these findings and discuss their implications.}, author = {Hannezo, Edouard B and Simons, Benjamin D.}, issn = {0012-1592}, journal = {Development Growth and Differentiation}, number = {9}, pages = {512--521}, publisher = {Wiley}, title = {{Statistical theory of branching morphogenesis}}, doi = {10.1111/dgd.12570}, volume = {60}, year = {2018}, } @article{5859, abstract = {The emergence of syntax during childhood is a remarkable example of how complex correlations unfold in nonlinear ways through development. In particular, rapid transitions seem to occur as children reach the age of two, which seems to separate a two-word, tree-like network of syntactic relations among words from the scale-free graphs associated with the adult, complex grammar. Here, we explore the evolution of syntax networks through language acquisition using the chromatic number, which captures the transition and provides a natural link to standard theories on syntactic structures. The data analysis is compared to a null model of network growth dynamics which is shown to display non-trivial and sensible differences. At a more general level, we observe that the chromatic classes define independent regions of the graph, and thus, can be interpreted as the footprints of incompatibility relations, somewhat as opposed to modularity considerations.}, author = {Corominas-Murtra, Bernat and Fibla, Martí Sànchez and Valverde, Sergi and Solé, Ricard}, issn = {2054-5703}, journal = {Royal Society Open Science}, number = {12}, publisher = {The Royal Society}, title = {{Chromatic transitions in the emergence of syntax networks}}, doi = {10.1098/rsos.181286}, volume = {5}, year = {2018}, } @article{401, abstract = {The actomyosin cytoskeleton, a key stress-producing unit in epithelial cells, oscillates spontaneously in a wide variety of systems. Although much of the signal cascade regulating myosin activity has been characterized, the origin of such oscillatory behavior is still unclear. Here, we show that basal myosin II oscillation in Drosophila ovarian epithelium is not controlled by actomyosin cortical tension, but instead relies on a biochemical oscillator involving ROCK and myosin phosphatase. Key to this oscillation is a diffusive ROCK flow, linking junctional Rho1 to medial actomyosin cortex, and dynamically maintained by a self-activation loop reliant on ROCK kinase activity. In response to the resulting myosin II recruitment, myosin phosphatase is locally enriched and shuts off ROCK and myosin II signals. Coupling Drosophila genetics, live imaging, modeling, and optogenetics, we uncover an intrinsic biochemical oscillator at the core of myosin II regulatory network, shedding light on the spatio-temporal dynamics of force generation.}, author = {Qin, Xiang and Hannezo, Edouard B and Mangeat, Thomas and Liu, Chang and Majumder, Pralay and Liu, Jjiaying and Choesmel Cadamuro, Valerie and Mcdonald, Jocelyn and Liu, Yinyao and Yi, Bin and Wang, Xiaobo}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{A biochemical network controlling basal myosin oscillation}}, doi = {10.1038/s41467-018-03574-5}, volume = {9}, year = {2018}, } @article{421, abstract = {Cell shape is determined by a balance of intrinsic properties of the cell as well as its mechanochemical environment. Inhomogeneous shape changes underlie many morphogenetic events and involve spatial gradients in active cellular forces induced by complex chemical signaling. Here, we introduce a mechanochemical model based on the notion that cell shape changes may be induced by external diffusible biomolecules that influence cellular contractility (or equivalently, adhesions) in a concentration-dependent manner—and whose spatial profile in turn is affected by cell shape. We map out theoretically the possible interplay between chemical concentration and cellular structure. Besides providing a direct route to spatial gradients in cell shape profiles in tissues, we show that the dependence on cell shape helps create robust mechanochemical gradients.}, author = {Dasbiswas, Kinjal and Hannezo, Claude-Edouard B and Gov, Nir}, journal = {Biophysical Journal}, number = {4}, pages = {968 -- 977}, publisher = {Biophysical Society}, title = {{Theory of eppithelial cell shape transitions induced by mechanoactive chemical gradients}}, doi = {10.1016/j.bpj.2017.12.022}, volume = {114}, year = {2018}, } @article{5860, abstract = {A major problem for evolutionary theory is understanding the so-called open-ended nature of evolutionary change, from its definition to its origins. Open-ended evolution (OEE) refers to the unbounded increase in complexity that seems to characterize evolution on multiple scales. This property seems to be a characteristic feature of biological and technological evolution and is strongly tied to the generative potential associated with combinatorics, which allows the system to grow and expand their available state spaces. Interestingly, many complex systems presumably displaying OEE, from language to proteins, share a common statistical property: the presence of Zipf's Law. Given an inventory of basic items (such as words or protein domains) required to build more complex structures (sentences or proteins) Zipf's Law tells us that most of these elements are rare whereas a few of them are extremely common. Using algorithmic information theory, in this paper we provide a fundamental definition for open-endedness, which can be understood as postulates. Its statistical counterpart, based on standard Shannon information theory, has the structure of a variational problem which is shown to lead to Zipf's Law as the expected consequence of an evolutionary process displaying OEE. We further explore the problem of information conservation through an OEE process and we conclude that statistical information (standard Shannon information) is not conserved, resulting in the paradoxical situation in which the increase of information content has the effect of erasing itself. We prove that this paradox is solved if we consider non-statistical forms of information. This last result implies that standard information theory may not be a suitable theoretical framework to explore the persistence and increase of the information content in OEE systems.}, author = {Corominas-Murtra, Bernat and Seoane, Luís F. and Solé, Ricard}, issn = {1742-5689}, journal = {Journal of the Royal Society Interface}, number = {149}, publisher = {Royal Society}, title = {{Zipf's Law, unbounded complexity and open-ended evolution}}, doi = {10.1098/rsif.2018.0395}, volume = {15}, year = {2018}, } @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}, } @article{726, abstract = {The morphogenesis of branched organs remains a subject of abiding interest. Although much is known about the underlying signaling pathways, it remains unclear how macroscopic features of branched organs, including their size, network topology, and spatial patterning, are encoded. Here, we show that, in mouse mammary gland, kidney, and human prostate, these features can be explained quantitatively within a single unifying framework of branching and annihilating random walks. Based on quantitative analyses of large-scale organ reconstructions and proliferation kinetics measurements, we propose that morphogenesis follows from the proliferative activity of equipotent tips that stochastically branch and randomly explore their environment but compete neutrally for space, becoming proliferatively inactive when in proximity with neighboring ducts. These results show that complex branched epithelial structures develop as a self-organized process, reliant upon a strikingly simple but generic rule, without recourse to a rigid and deterministic sequence of genetically programmed events.}, author = {Hannezo, Edouard B and Scheele, Colinda and Moad, Mohammad and Drogo, Nicholas and Heer, Rakesh and Sampogna, Rosemary and Van Rheenen, Jacco and Simons, Benjamin}, issn = {0092-8674}, journal = {Cell}, number = {1}, pages = {242 -- 255}, publisher = {Cell Press}, title = {{A unifying theory of branching morphogenesis}}, doi = {10.1016/j.cell.2017.08.026}, volume = {171}, year = {2017}, }