TY - JOUR AB - 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. AU - Yang, Qiutan AU - Xue, Shi-lei AU - Chan, Chii Jou AU - Rempfler, Markus AU - Vischi, Dario AU - Maurer-Gutierrez, Francisca AU - Hiiragi, Takashi AU - Hannezo, Edouard B AU - Liberali, Prisca ID - 9629 JF - Nature Cell Biology SN - 1465-7392 TI - Cell fate coordinates mechano-osmotic forces in intestinal crypt formation VL - 23 ER - TY - JOUR AB - 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. AU - Tavano, Ste AU - Heisenberg, Carl-Philipp J ID - 6837 IS - 8 JF - Nature Cell Biology TI - Migrasomes take center stage VL - 21 ER - TY - JOUR AB - 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. AU - Yolland, Lawrence AU - Burki, Mubarik AU - Marcotti, Stefania AU - Luchici, Andrei AU - Kenny, Fiona N. AU - Davis, John Robert AU - Serna-Morales, Eduardo AU - Müller, Jan AU - Sixt, Michael K AU - Davidson, Andrew AU - Wood, Will AU - Schumacher, Linus J. AU - Endres, Robert G. AU - Miodownik, Mark AU - Stramer, Brian M. ID - 7105 IS - 11 JF - Nature Cell Biology SN - 1465-7392 TI - Persistent and polarized global actin flow is essential for directionality during cell migration VL - 21 ER - TY - JOUR AB - 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. AU - Anderson, Daniel J. AU - HETZER, Martin W ID - 11115 IS - 10 JF - Nature Cell Biology KW - Cell Biology SN - 1465-7392 TI - Nuclear envelope formation by chromatin-mediated reorganization of the endoplasmic reticulum VL - 9 ER - TY - JOUR AB - 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. AU - HETZER, Martin W AU - Gruss, Oliver J. AU - Mattaj, Iain W. ID - 11123 IS - 7 JF - Nature Cell Biology KW - Cell Biology SN - 1465-7392 TI - The Ran GTPase as a marker of chromosome position in spindle formation and nuclear envelope assembly VL - 4 ER - TY - JOUR AB - 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. AU - HETZER, Martin W AU - Meyer, Hemmo H. AU - Walther, Tobias C. AU - Bilbao-Cortes, Daniel AU - Warren, Graham AU - Mattaj, Iain W. ID - 11125 IS - 12 JF - Nature Cell Biology KW - Cell Biology SN - 1465-7392 TI - Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assembly VL - 3 ER -