@article {68715, title = {Extracellular matrix assembly stress initiates Drosophila central nervous system morphogenesis.}, journal = {Developmental Cell}, year = {2023}, month = {2023 Apr 17}, abstract = {

Forces controlling tissue morphogenesis are attributed to cellular-driven activities, and any role for extracellular matrix (ECM) is assumed to be passive. However, all polymer networks, including ECM, can develop autonomous stresses during their assembly. Here, we examine the morphogenetic function of an ECM before reaching homeostatic equilibrium by analyzing de novo ECM assembly during Drosophila ventral nerve cord (VNC) condensation. Asymmetric VNC shortening and a rapid decrease in surface area correlate with the exponential assembly of collagen IV (Col4) surrounding the tissue. Concomitantly, a transient developmentally induced Col4 gradient leads to coherent long-range flow of ECM, which equilibrates the Col4 network. Finite element analysis and perturbation of Col4 network formation through the generation of dominant Col4 mutations that affect assembly reveal that VNC morphodynamics is partially driven by a sudden increase in ECM-driven surface tension. These data suggest that ECM assembly stress and associated network instabilities can actively participate in tissue morphogenesis.

}, issn = {1878-1551}, doi = {10.1016/j.devcel.2023.03.019}, author = {Serna-Morales, Eduardo and S{\'a}nchez-S{\'a}nchez, Besaiz J and Marcotti, Stefania and Nichols, Angus and Bhargava, Anushka and Dragu, Anca and Hirvonen, Liisa M and Diaz-de-la-Loza, Maria-Del-Carmen and Mink, Matyas and Cox, Susan and Rayfield, Emily and Lee, Rachel M and Hobson, Chad M and Chew, Teng-Leong and Stramer, Brian M} } @article {68784, title = {Extracellular matrix assembly stress initiates Drosophila central nervous system morphogenesis.}, journal = {Developmental Cell}, volume = {58}, year = {2023}, month = {2023 May 22}, pages = {825-835.e6}, abstract = {

Forces controlling tissue morphogenesis are attributed to cellular-driven activities, and any role for extracellular matrix (ECM) is assumed to be passive. However, all polymer networks, including ECM, can develop autonomous stresses during their assembly. Here, we examine the morphogenetic function of an ECM before reaching homeostatic equilibrium by analyzing de novo ECM assembly during Drosophila ventral nerve cord (VNC) condensation. Asymmetric VNC shortening and a rapid decrease in surface area correlate with the exponential assembly of collagen IV (Col4) surrounding the tissue. Concomitantly, a transient developmentally induced Col4 gradient leads to coherent long-range flow of ECM, which equilibrates the Col4 network. Finite element analysis and perturbation of Col4 network formation through the generation of dominant Col4 mutations that affect assembly reveal that VNC morphodynamics is partially driven by a sudden increase in ECM-driven surface tension. These data suggest that ECM assembly stress and associated network instabilities can actively participate in tissue morphogenesis.

}, keywords = {Animals, Central Nervous System, Drosophila, Extracellular Matrix, Morphogenesis}, issn = {1878-1551}, doi = {10.1016/j.devcel.2023.03.019}, author = {Serna-Morales, Eduardo and S{\'a}nchez-S{\'a}nchez, Besaiz J and Marcotti, Stefania and Nichols, Angus and Bhargava, Anushka and Dragu, Anca and Hirvonen, Liisa M and Diaz-de-la-Loza, Maria-Del-Carmen and Mink, Matyas and Cox, Susan and Rayfield, Emily and Lee, Rachel M and Hobson, Chad M and Chew, Teng-Leong and Stramer, Brian M} } @article {65602, title = {FMNL2 regulates dynamics of fascin in filopodia.}, journal = {Journal of Cell Biology}, volume = {219}, year = {2020}, month = {2020 May 04}, abstract = {

Filopodia are peripheral F-actin-rich structures that enable cell sensing of the microenvironment. Fascin is an F-actin-bundling protein that plays a key role in stabilizing filopodia to support efficient adhesion and migration. Fascin is also highly up-regulated in human cancers, where it increases invasive cell behavior and correlates with poor patient prognosis. Previous studies have shown that fascin phosphorylation can regulate F-actin bundling, and that this modification can contribute to subcellular fascin localization and function. However, the factors that regulate fascin dynamics within filopodia remain poorly understood. In the current study, we used advanced live-cell imaging techniques and a fascin biosensor to demonstrate that fascin phosphorylation, localization, and binding to F-actin are highly dynamic and dependent on local cytoskeletal architecture in cells in both 2D and 3D environments. Fascin dynamics within filopodia are under the control of formins, and in particular FMNL2, that binds directly to dephosphorylated fascin. Our data provide new insight into control of fascin dynamics at the nanoscale and into the mechanisms governing rapid cytoskeletal adaptation to environmental changes. This filopodia-driven exploration stage may represent an essential regulatory step in the transition from static to migrating cancer cells.

}, issn = {1540-8140}, doi = {10.1083/jcb.201906111}, author = {Pfisterer, Karin and Levitt, James and Lawson, Campbell D and Marsh, Richard J and Heddleston, John M and Wait, Eric and Ameer-Beg, Simon Morris and Cox, Susan and Parsons, Maddy} } @article {47661, title = {Bayesian localization microscopy reveals nanoscale podosome dynamics.}, journal = {Nature methods}, volume = {9}, year = {2012}, month = {2012 Feb}, pages = {195-200}, abstract = {

We describe a localization microscopy analysis method that is able to extract results in live cells using standard fluorescent proteins and xenon arc lamp illumination. Our Bayesian analysis of the blinking and bleaching (3B analysis) method models the entire dataset simultaneously as being generated by a number of fluorophores that may or may not be emitting light at any given time. The resulting technique allows many overlapping fluorophores in each frame and unifies the analysis of the localization from blinking and bleaching events. By modeling the entire dataset, we were able to use each reappearance of a fluorophore to improve the localization accuracy. The high performance of this technique allowed us to reveal the nanoscale dynamics of podosome formation and dissociation throughout an entire cell with a resolution of 50 nm on a 4-s timescale.

}, keywords = {Bayes Theorem, Cell Line, Tumor, Humans, Nanotechnology}, issn = {1548-7105}, doi = {10.1038/nmeth.1812}, author = {Cox, Susan and Rosten, Edward and Monypenny, James and Jovanovic-Talisman, Tijana and Burnette, Dylan T and Lippincott-Schwartz, Jennifer and Jones, Gareth E and Heintzmann, Rainer} }