Strength of interactions in the Notch gene regulatory network determines patterning and fate in the notochord

Development of multicellular organisms requires the generation of gene expression patterns that determines cell fate and organ shape. Groups of genetic interactions known as Gene Regulatory Networks (GRNs) play a key role in the generation of such patterns. However, how the topology and parameters of GRNs determine patterning in vivo remains unclear due to the complexity of most experimental systems. To address this, we use the zebrafish notochord, an organ where coin-shaped precursor cells are initially arranged in a simple unidimensional geometry. These cells then differentiate into vacuolated and sheath cells. Using newly developed transgenic tools together with in vivo imaging, we identify jag1a and her6/her9 as the main components of a Notch GRN that generates a lateral inhibition pattern and determines cell fate. Making use of this experimental system and mathematical modeling we show that lateral inhibition patterning is promoted when ligand-receptor interactions are stronger within the same cell than in neighboring cells. Altogether, we establish the zebrafish notochord as an experimental system to study pattern generation, and identify and characterize how the properties of GRNs determine self-organization of gene patterning and cell fate

Control of Directed Cell Migration In Vivo by Membrane-to-Cortex Attachment

Analysis of cell migration in vivo combined with biophysical measurements reveals how membrane-to-cortex attachment fine-tunes the type of protrusions formed by cells and, as a consequence, controls directed migration during zebrafish gastrulation

Steering cell migration by alternating blebs and actin-rich protrusions.

BACKGROUND: High directional persistence is often assumed to enhance the efficiency of chemotactic migration. Yet, cells in vivo usually display meandering trajectories with relatively low directional persistence, and the control and function of directional persistence during cell migration in three-dimensional environments are poorly understood. RESULTS: Here, we use mesendoderm progenitors migrating during zebrafish gastrulation as a model system to investigate the control of directional persistence during migration in vivo. We show that progenitor cells alternate persistent run phases with tumble phases that result in cell reorientation. Runs are characterized by the formation of directed actin-rich protrusions and tumbles by enhanced blebbing. Increasing the proportion of actin-rich protrusions or blebs leads to longer or shorter run phases, respectively. Importantly, both reducing and increasing run phases result in larger spatial dispersion of the cells, indicative of reduced migration precision. A physical model quantitatively recapitulating the migratory behavior of mesendoderm progenitors indicates that the ratio of tumbling to run times, and thus the specific degree of directional persistence of migration, are critical for optimizing migration precision. CONCLUSIONS: Together, our experiments and model provide mechanistic insight into the control of migration directionality for cells moving in three-dimensional environments that combine different protrusion types, whereby the proportion of blebs to actin-rich protrusions determines the directional persistence and precision of movement by regulating the ratio of tumbling to run times.This work was supported by the Max Planck Society, the Medical Research Council UK (core funding to the MRC LMCB), and by grants from the Polish Ministry of Science and Higher Education (454/N-MPG/2009/0) to EKP, the Deutsche Forschungsgemeinschaft (HE 3231/6-1 and PA 1590/1-1) to CPH and EKP, a A*Star JCO career development award (12302FG010) to WY and a Damon Runyon fellowship award to ADM (DRG 2157-12). This work was also supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001317), the UK Medical Research Council (FC001317), and the Wellcome Trust (FC001317) to G

In vivo function of the lipid raft protein flotillin-1 during cd8+ t cell–mediated host surveillance

Flotillin-1 (Flot1) is an evolutionary conserved, ubiquitously expressed lipid raft– associated scaffolding protein. Migration of Flot1-deficient neutrophils is impaired because of a decrease in myosin II–mediated contractility. Flot1 also accumulates in the uropod of polarized T cells, suggesting an analogous role in T cell migration. In this study, we analyzed morphology and migration parameters of murine wild-type and Flot1−/− CD8+ T cells using in vitro assays and intravital two-photon microscopy of lymphoid and nonlymphoid tissues. Flot1−/− CD8+ T cells displayed significant alterations in cell shape and motility parameters in vivo but showed comparable homing to lymphoid organs and intact in vitro migration to chemokines. Furthermore, their clonal expansion and infiltration into nonlymphoid tissues during primary and secondary antiviral immune responses was comparable to wild-type CD8+ T cells. Taken together, Flot1 plays a detectable but unexpectedly minor role for CD8+ T cell behavior under physiological conditions

Biophysics across time and space

Understanding the behaviour of almost any biological object is a fundamentally multiscale problem — a challenge that biophysicists have been increasingly embracing, building on two centuries of biophysical studies at a variety of length scales

Entrevistas a artistas y formatos de interacción. Red para el intercambio de conocimientos y experiencias entre artistas y conservadores-restauradores

Este proyecto ha tenido como objetivo la creación de una red interdisciplinar, internivelar, interdepartamental e interfacultativa de profesores, estudiantes y alumni de las áreas de Bellas Artes, Conservación-Restauración y Diseño de la Universidad Complutense de Madrid y de la Universidad de La Laguna. El presente proyecto surge de la necesidad constatada durante el contexto del COVID-19 de proporcionar nuevas herramientas a los estudiantes que les permitan desarrollar las competencias que sus titulaciones establecen y de fortalecer el tejido de interacciones transdisciplinares dentro de la Facultad de Bellas Artes. A través de una convocataoria pública a artistas y de una reflexión en torno a la metodología de entrevista al artista en conservación-restauración de arte contemporáneo, se han desarrollado dinámicas interdisciplinares y estrategias de enseñanza-aprendizaje horizontales entre artistas, profesores y estudiantes de distintos niveles (grado, postgrado, doctorado) como fórmula para amplificar la generación de conocimiento en la universidad. El proyecto ha abarcado la dirección de TFGs, el desarrollo de una investigación en torno a nuevos formatos de interacción entre conservadores-restauradores y artistas, y el desarrollo de dos seminarios públicos. Esta memoria recoge los objetivos propuestos y evalúa los alcanzados en base a una serie de indicadores, describe la metodología utilizada en el proyecto, analiza las características del equipo de trabajo y expone las actividades desarrolladas durante el curso 2020-2021. Los Anexos incluyen documentación sobre las actividades desarrolladas e imágenes sobre los procesos de investigación

Myosin light chain kinase regulates cell polarization independently of membrane tension or Rho kinase

Cells polarize to a single front and rear to achieve rapid actin-based motility, but the mechanisms preventing the formation of multiple fronts are unclear. We developed embryonic zebrafish keratocytes as a model system for investigating establishment of a single axis. We observed that, although keratocytes from 2 d postfertilization (dpf) embryos resembled canonical fan-shaped keratocytes, keratocytes from 4 dpf embryos often formed multiple protrusions despite unchanged membrane tension. Using genomic, genetic, and pharmacological approaches, we determined that the multiple-protrusion phenotype was primarily due to increased myosin light chain kinase (MLCK) expression. MLCK activity influences cell polarity by increasing myosin accumulation in lamellipodia, which locally decreases protrusion lifetime, limiting lamellipodial size and allowing for multiple protrusions to coexist within the context of membrane tension limiting protrusion globally. In contrast, Rho kinase (ROCK) regulates myosin accumulation at the cell rear and does not determine protrusion size. These results suggest a novel MLCK-specific mechanism for controlling cell polarity via regulation of myosin activity in protrusions

Entre artistas y restauradorӕs. Nuevos formatos de interacción e intercambio de conocimiento

Este proyecto ha tenido como objetivo la consolidación de una red de cooperación horizontal e intercambio interdisciplinar, internivelar, interdepartamental e interfacultativa entre artistas y conservadoræs-restauradoræs, así como la exploración de nuevas formas de interacción para generar conocimiento. Esta red conecta entre sí a los departamentos de la Facultad de Bellas Artes de la UCM (Dibujo y Grabado; Diseño e Imagen; y Pintura y Conservación-Restauración), al tiempo que fomenta interacciones con estudiantes y docentes de departamentos de arte y conservación-restauración de otras universidades públicas y privadas como son la Universidad de la Laguna, la Universidad Politécnica de Madrid, la Universidad Francisco de Vitoria y la Universidad Antonio Nebrija. Así mismo, incorpora a la red un organismo externo al ámbito de la universidad y vinculado al ámbito profesional de la práctica artística, como es la Asociación Cultural Atelier Solar. El proyecto ha abarcado la realización de tres encuentros, un curso, una mesa redonda, la dirección de TFGs, la visita a estudios de artistas y el desarrollo de una investigación en torno a nuevos formatos de interacción entre conservadoræs-restauradoræs y artistas. Esta memoria recoge los objetivos propuestos y evalúa los alcanzados en base a una serie de indicadores, describe la metodología utilizada en el proyecto, analiza las características del equipo de trabajo y expone las actividades desarrolladas durante el curso 2021-2022. Los Anexos incluyen documentación sobre las actividades desarrolladas e imágenes sobre los procesos de investigación

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

PhDAY 2020 -FOO (Facultad de Óptica y Optometría)

Por cuarto año consecutivo los doctorandos de la Facultad de Óptica y Optometría de la Universidad Complutense de Madrid cuentan con un congreso propio organizado por y para ellos, el 4º PhDAY- FOO. Se trata de un congreso gratuito abierto en la que estos jóvenes científicos podrán presentar sus investigaciones al resto de sus compañeros predoctorales y a toda la comunidad universitaria que quiera disfrutar de este evento. Apunta en tu agenda: el 15 de octubre de 2020. En esta ocasión será un Congreso On-line para evitar que la incertidumbre asociada a la pandemia Covid-19 pudiera condicionar su celebración