@article{22720, abstract = {Circadian clocks underlie daily rhythms in physiology by coordinating temporal patterns of gene expression and protein function throughout the body. At the core of this system in mammals is CLOCK/BMAL1, a ubiquitously expressed heterodimeric transcription factor complex that orchestrates tissue-specific circadian gene expression. The basis for this specificity remains unclear, but tissue-specific interactions at chromatin could provide one. Here we used chromatin immunoprecipitation coupled to mass spectrometry to map CLOCK/BMAL1-associated protein complexes on chromatin in mouse liver, kidney and lung. We detected 1,510 associated proteins, most of which were tissue-specific and not explained by protein abundance. Among these, we identified the homeodomain transcription factors PROX1, HNF1B and HOXA5 as tissue-enriched interactors that bind BMAL1, co-occupy most BMAL1 genomic sites and establish organ-restricted circadian transcription. Our findings demonstrate that tissue-specific transcription factors confer cellular identity on the core clock, thereby contributing to organ-specific patterns of rhythmic gene expression.}, author = {Aygenli, Fatih and Huschet, Lukas A. and Popp, Tanja and Ribeiro, Andrea and Barkhatova, Darina and Jouffe, Céline and Trozzo, Ricardo and Menet, Jerome S. and Rad, Roland and Dyar, Kenneth A. and Lech, Maciej and Straub, Tobias and Michael, Alicia and Robles, Maria S.}, issn = {1476-4679}, journal = {Nature Cell Biology}, publisher = {Springer Nature}, title = {{CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators}}, doi = {10.1038/s41556-026-02041-4}, year = {2026}, } @article{9629, abstract = {Intestinal organoids derived from single cells undergo complex crypt–villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Here, using light-sheet microscopy and large-scale imaging quantification, we demonstrate that crypt formation coincides with a stark reduction in lumen volume. We develop a 3D biophysical model to computationally screen different mechanical scenarios of crypt morphogenesis. Combining this with live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven crypt apical contraction and villus basal tension work synergistically with lumen volume reduction to drive crypt morphogenesis, and demonstrate the existence of a critical point in differential tensions above which crypt morphology becomes robust to volume changes. Finally, we identified a sodium/glucose cotransporter that is specific to differentiated enterocytes that modulates lumen volume reduction through cell swelling in the villus region. Together, our study uncovers the cellular basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust morphogenesis.}, author = {Yang, Qiutan and Xue, Shi-lei and Chan, Chii Jou and Rempfler, Markus and Vischi, Dario and Maurer-Gutierrez, Francisca and Hiiragi, Takashi and Hannezo, Edouard B and Liberali, Prisca}, issn = {1476-4679}, journal = {Nature Cell Biology}, pages = {733–744}, publisher = {Springer Nature}, title = {{Cell fate coordinates mechano-osmotic forces in intestinal crypt formation}}, doi = {10.1038/s41556-021-00700-2}, volume = {23}, year = {2021}, } @article{6837, abstract = {Migrasomes are a recently discovered type of extracellular vesicles that are characteristically generated along retraction fibers in migrating cells. Two studies now show how migrasomes are formed and how they function in the physiologically relevant context of the developing zebrafish embryo.}, author = {Tavano, Ste and Heisenberg, Carl-Philipp J}, issn = {1476-4679}, journal = {Nature Cell Biology}, number = {8}, pages = {918--920}, publisher = {Springer Nature}, title = {{Migrasomes take center stage}}, doi = {10.1038/s41556-019-0369-3}, volume = {21}, year = {2019}, } @article{7105, abstract = {Cell migration is hypothesized to involve a cycle of behaviours beginning with leading edge extension. However, recent evidence suggests that the leading edge may be dispensable for migration, raising the question of what actually controls cell directionality. Here, we exploit the embryonic migration of Drosophila macrophages to bridge the different temporal scales of the behaviours controlling motility. This approach reveals that edge fluctuations during random motility are not persistent and are weakly correlated with motion. In contrast, flow of the actin network behind the leading edge is highly persistent. Quantification of actin flow structure during migration reveals a stable organization and asymmetry in the cell-wide flowfield that strongly correlates with cell directionality. This organization is regulated by a gradient of actin network compression and destruction, which is controlled by myosin contraction and cofilin-mediated disassembly. It is this stable actin-flow polarity, which integrates rapid fluctuations of the leading edge, that controls inherent cellular persistence.}, author = {Yolland, Lawrence and Burki, Mubarik and Marcotti, Stefania and Luchici, Andrei and Kenny, Fiona N. and Davis, John Robert and Serna-Morales, Eduardo and Müller, Jan and Sixt, Michael K and Davidson, Andrew and Wood, Will and Schumacher, Linus J. and Endres, Robert G. and Miodownik, Mark and Stramer, Brian M.}, issn = {1476-4679}, journal = {Nature Cell Biology}, number = {11}, pages = {1370--1381}, publisher = {Springer Nature}, title = {{Persistent and polarized global actin flow is essential for directionality during cell migration}}, doi = {10.1038/s41556-019-0411-5}, volume = {21}, year = {2019}, } @article{4181, abstract = {Understanding the factors that direct tissue organization during development is one of the most fundamental goals in developmental biology. Various hypotheses explain cell sorting and tissue organization on the basis of the adhesive and mechanical properties of the constituent cells(1). However, validating these hypotheses has been difficult due to the lack of appropriate tools to measure these parameters. Here we use atomic force microscopy ( AFM) to quantify the adhesive and mechanical properties of individual ectoderm, mesoderm and endoderm progenitor cells from gastrulating zebrafish embryos. Combining these data with tissue self-assembly in vitro and the sorting behaviour of progenitors in vivo, we have shown that differential actomyosin-dependent cell-cortex tension, regulated by Nodal/ TGF beta-signalling ( transforming growth factor beta), constitutes a key factor that directs progenitor-cell sorting. These results demonstrate a previously unrecognized role for Nodal-controlled cell-cortex tension in germ-layer organization during gastrulation.}, author = {Krieg, Michael and Arboleda Estudillo, Yohanna and Puech, Pierre and Käfer, Jos and Graner, François and Mueller, Daniel and Heisenberg, Carl-Philipp J}, issn = {1476-4679}, journal = {Nature Cell Biology}, number = {4}, pages = {429 -- 436}, publisher = {Nature Publishing Group}, title = {{Tensile forces govern germ-layer organization in zebrafish}}, doi = {10.1038/ncb1705}, volume = {10}, year = {2008}, } @article{11115, abstract = {The formation of the nuclear envelope (NE) around chromatin is a major membrane-remodelling event that occurs during cell division of metazoa. It is unclear whether the nuclear membrane reforms by the fusion of NE fragments or if it re-emerges from an intact tubular network of the endoplasmic reticulum (ER). Here, we show that NE formation and expansion requires a tubular ER network and occurs efficiently in the presence of the membrane fusion inhibitor GTPγS. Chromatin recruitment of membranes, which is initiated by tubule-end binding, followed by the formation, expansion and sealing of flat membrane sheets, is mediated by DNA-binding proteins residing in the ER. Thus, chromatin plays an active role in reshaping of the ER during NE formation.}, author = {Anderson, Daniel J. and HETZER, Martin W}, issn = {1476-4679}, journal = {Nature Cell Biology}, keywords = {Cell Biology}, number = {10}, pages = {1160--1166}, publisher = {Springer Nature}, title = {{Nuclear envelope formation by chromatin-mediated reorganization of the endoplasmic reticulum}}, doi = {10.1038/ncb1636}, volume = {9}, year = {2007}, } @article{3150, abstract = {Tripartite G-protein-coupled receptors (GPCRs) represent one of the largest groups of signal transducers, transmitting signals from hormones, neuropeptides, odorants, food and light. Ligand-bound receptors catalyse GDP/GTP exchange on the G-protein α-subunit (Gα), leading to α-GTP separation from the βγ subunits and pathway activation. Activating mutations in the receptors or G proteins underlie many human diseases, including some cancers, dwarfism and premature puberty. Regulators of G-protein signalling (RGS proteins) are known to modulate the level and duration of ligand-induced signalling by accelerating the intrinsic GTPase activity of the Gα subunit, and thus reformation of the inactive GDP-bound Gα. Here we find that even in the absence of receptor, mutation of the RGS family member Sst2 (refs 6-9) permits spontaneous activation of the G-protein-coupled mating pathway in Saccharomyces cerevisiae at levels normally seen only in the presence of ligand. Our work demonstrates the occurence of spontaneous tripartite G-protein signalling in vivo and identifies a requirement for RGS proteins in preventing such receptor-independent activation.}, author = {Siekhaus, Daria E and Drubin, David}, issn = {1476-4679}, journal = {Nature Cell Biology}, number = {3}, pages = {231 -- 235}, publisher = {Springer Nature}, title = {{Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant}}, doi = {10.1038/ncb941}, volume = {5}, year = {2003}, } @article{11123, abstract = {The small GTPase Ran is a key regulator of nucleocytoplasmic transport during interphase. The asymmetric distribution of the GTP-bound form of Ran across the nuclear envelope — that is, large quantities in the nucleus compared with small quantities in the cytoplasm — determines the directionality of many nuclear transport processes. Recent findings that Ran also functions in spindle formation and nuclear envelope assembly during mitosis suggest that Ran has a general role in chromatin-centred processes. Ran functions in these events as a signal for chromosome position.}, author = {HETZER, Martin W and Gruss, Oliver J. and Mattaj, Iain W.}, issn = {1476-4679}, journal = {Nature Cell Biology}, keywords = {Cell Biology}, number = {7}, pages = {E177--E184}, publisher = {Springer Nature}, title = {{The Ran GTPase as a marker of chromosome position in spindle formation and nuclear envelope assembly}}, doi = {10.1038/ncb0702-e177}, volume = {4}, year = {2002}, } @article{11125, abstract = {Although nuclear envelope (NE) assembly is known to require the GTPase Ran, the membrane fusion machinery involved is uncharacterized. NE assembly involves formation of a reticular network on chromatin, fusion of this network into a closed NE and subsequent expansion. Here we show that p97, an AAA-ATPase previously implicated in fusion of Golgi and transitional endoplasmic reticulum (ER) membranes together with the adaptor p47, has two discrete functions in NE assembly. Formation of a closed NE requires the p97–Ufd1–Npl4 complex, not previously implicated in membrane fusion. Subsequent NE growth involves a p97–p47 complex. This study provides the first insights into the molecular mechanisms and specificity of fusion events involved in NE formation.}, author = {HETZER, Martin W and Meyer, Hemmo H. and Walther, Tobias C. and Bilbao-Cortes, Daniel and Warren, Graham and Mattaj, Iain W.}, issn = {1476-4679}, journal = {Nature Cell Biology}, keywords = {Cell Biology}, number = {12}, pages = {1086--1091}, publisher = {Springer Nature}, title = {{Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assembly}}, doi = {10.1038/ncb1201-1086}, volume = {3}, year = {2001}, }