https://hdl.handle.net/2072/478780 Mon, 06 Apr 2026 12:09:11 GMT 2026-04-06T12:09:11Z https://hdl.handle.net/2445/228537 Cortex folding by combined progenitor expansion and adhesion-controlled neuronal migration Chun, Seung Hee; Yoon, Da Eun; Diaz Almeida, Daniel Santiago; Todorov, Mihail Ivilinov; Straub, Tobias; Ruff, Tobias; Shao, Wei; Yang, Jianjun; Seyit Bremer, Gönül; Shen, Yi-Ru; Ertürk, Ali; Toro Ruiz, Daniel del; Shi, Songhai; Klein, Rüdiger Folding of the mammalian cerebral cortex into sulcal fissures and gyral peaks is the result of complex processes that are incompletely understood. Previously we showed that genetic deletion of Flrt1/3 adhesion molecules causes folding of the smooth mouse cortex into sulci resulting from increased lateral dispersion and faster neuron migration, without progenitor expansion. Here, we show in mice that combining the Flrt1/3 double knockout with an additional genetic deletion that causes progenitor expansion, greatly enhances cortex folding. Expansion of intermediate progenitors by deletion of Cep83 leads to a relative increase in Flrt-mutant neurons resulting in enhanced formation of sulci. Expansion of apical progenitors by deletion of Fgf10 leads to a relative reduction in Flrt-mutant neurons resulting in enhanced formation of gyri. These results together with computational modeling identify key developmental mechanisms, such as adhesive properties, cell densities and migration of cortical neurons, that cooperate to promote cortical gyrification. Thu, 26 Mar 2026 15:56:08 GMT https://hdl.handle.net/2445/228537 2026-03-26T15:56:08Z https://hdl.handle.net/2445/228531 Identification of a crosstalk between ClC-1 C-terminal CBS domains and the transmembrane region Gaitán-Peñas, Héctor; Pérez González, Anna Priscil·la; González Subías, Marc; Zdebik, Anselm A.; Gasull Casanova, Xavier; Buey, Ruben M.; Errasti-Murugarren, Ekaitz; Estévez Povedano, Raúl CLC channels and transporters have large C-terminal regions which contain two cystathionine β-synthetase (CBS) domains. It has been hypothesized that conformational changes in these domains upon nucleotide binding modulate the gating of the CLC dimer. It is not clear how rearrangements that occur in the CBS domains are transmitted to the ion pathway, as CBS domains interact with the rest of the channel at multiple locations and some of these sites are not visible in recent solved cryogenic electron microscopy structures or are difficult to model using the AlphaFold server. Using ClC-1 as a model, we started working with a described ClC-1 mutation (H835R) located in the first alpha helix of the CBS2 domain which changes the voltage dependence of gating. We then identified several residues located in the disorganized loop after helix R (R-linker) that revert the phenotype of this mutation. We additionally proved that R-linker's function is connected to the CBS2 domain as current intensity, plasma membrane levels and gating defects of several R-linker variants were corrected by adding the mutation H835R. Furthermore, cross-linking studies using newly developed split-cysless ClC-1 channels containing specific cysteine mutants in the R-linker and the CBS2 domain indicate that these two regions are in close contact. Considering these new results, we propose that conformational changes occurring in the CBS domains could be transmitted to the CLC intracellular chloride binding site by means of its interaction with the R-linker. Thu, 26 Mar 2026 13:55:39 GMT https://hdl.handle.net/2445/228531 2026-03-26T13:55:39Z https://hdl.handle.net/2445/228245 Protocol for tailored in vitro neuronal networks on high-density microelectrode arrays with polydimethylsiloxane microstructures Haeb, Anna-Christina; Yamamoto, Hideaki; Roach, Paul; Merryweather, Daniel; Sato, Y.; Tornero, Daniel; Soriano i Fradera, Jordi Complementary metal-oxide-semiconductor (CMOS)-based high-density microelectrode arrays (HD-MEAs) enable neuronal recordings with high spatiotemporal resolution. However, integrating polydimethylsiloxane (PDMS) microstructures onto HD-MEA surfaces to control network architecture is currently challenging and platform specific. Here, we present a protocol for PDMS fabrication, HD-MEA chip preparation, PDMS-HD-MEA microstructure alignment, and cell culture, including alternatives. Our results show reproducible formation of modular networks with characteristic activity patterns across different systems. This protocol supports engineering of defined neuronal architectures while maintaining compatibility with various HD-MEA systems. Wed, 18 Mar 2026 08:32:26 GMT https://hdl.handle.net/2445/228245 2026-03-18T08:32:26Z https://hdl.handle.net/2445/228065 Active wetting of epithelial tissues Pérez González, Carlos; Alert Zenón, Ricard; Blanch Mercader, Carles; Gómez González, Manuel; Kolodziej, Tomasz; Bazellières, Elsa; Casademunt i Viader, Jaume; Trepat Guixer, Xavier Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behaviour of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between two-dimensional epithelial monolayers and three-dimensional spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell-cell and cell-substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic length scale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting¿a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumour progression. Fri, 13 Mar 2026 08:46:12 GMT https://hdl.handle.net/2445/228065 2026-03-13T08:46:12Z