Predicting Apoptosis Engagement Downstream of Caspases in vivo
Epithelial cell death is widespread during development and tissue homeostasis. While the core pathway of apoptosis is well known, we lack predictive power to understand when and where a specific cell will die in a tissue. Yet, thi...
Epithelial cell death is widespread during development and tissue homeostasis. While the core pathway of apoptosis is well known, we lack predictive power to understand when and where a specific cell will die in a tissue. Yet, this should have important consequences for clone selection and tissue homeostasis, as exemplified by the process of cell competition. This context dependent cell elimination is essential for tissue homeostasis and tumour progression, but we know very little about its prevalence during normal development. Recent works have characterised multiple non-apoptotic functions of effector caspases and a high frequency of cells undergoing transient caspase activation without death. Yet, what distinguishes a dying from a surviving cell downstream of effector caspase activation is completely unknown. Using quantitative live imaging of effector caspase sensors and caspase activity tuning by optogenetics in the Drosophila pupal notum (a single layer epithelium), we found that cells engage in apoptosis at very variable levels of effector caspase activity. This suggested that the engagement in apoptosis can be developmentally modulated downstream of the most terminal caspase activation and that a completely new layer of regulation of cell death could have important physiological roles. Here, we propose to combine quantitative live imaging, multivariate model, supervised machine learning and quantitative perturbations through optogenetics to define parameters predictive of the engagement in apoptosis downstream of caspase activation. We will then use spatial omics combined with an optogenetic based screening to identify new factors modulating the sensitivity to caspases. Eventually we will unravel the physiological functions of caspase sensitivity modulation by defining a new paradigm of physiological cell competition and clone selection, and characterising its impact on tissue morphogenesis and oncogenic cell elimination.ver más
Seleccionando "Aceptar todas las cookies" acepta el uso de cookies para ayudarnos a brindarle una mejor experiencia de usuario y para analizar el uso del sitio web. Al hacer clic en "Ajustar tus preferencias" puede elegir qué cookies permitir. Solo las cookies esenciales son necesarias para el correcto funcionamiento de nuestro sitio web y no se pueden rechazar.
Cookie settings
Nuestro sitio web almacena cuatro tipos de cookies. En cualquier momento puede elegir qué cookies acepta y cuáles rechaza. Puede obtener más información sobre qué son las cookies y qué tipos de cookies almacenamos en nuestra Política de cookies.
Son necesarias por razones técnicas. Sin ellas, este sitio web podría no funcionar correctamente.
Son necesarias para una funcionalidad específica en el sitio web. Sin ellos, algunas características pueden estar deshabilitadas.
Nos permite analizar el uso del sitio web y mejorar la experiencia del visitante.
Nos permite personalizar su experiencia y enviarle contenido y ofertas relevantes, en este sitio web y en otros sitios web.