%0 Thesis
%A Sousa Ortega, Ana
%T A Yap-dependent mechano-regulatory loop directs cell migration for embryo axis assembly
%D 2023
%U http://hdl.handle.net/10433/16654
%X Gastrulation is a decisive process that occurs during embryonic development, in whicha relatively homogenous group of cells is transformed into an embryo with establishedbody axes and presenting the three germ layers. This is achieved through complex cellrearrangements that are tightly controlled by the interplay of the different types ofmorphogenetic inputs. In the animal kingdom, striking divergences exist in embryonicdevelopment, as they evolve and adapt to different environments, egg architecture andspeed of development. However, even though large differences can be found amongthe different species, the underlying logic and principles governing the gastrulationmovements are conserved. The set of cell movements observed during gastrulation isnot exclusive to this process, as they are also generally involved in organogenesis, tissueregeneration, and cancer progression. Therefore, understanding how the gastrulationmovements are coordinated and controlled is essential not only to understand axisformation, but also how tissues and organs are build, and even which are the mechanismunderlying oncogenic growth and metastasis. The key role of mechanical inputs duringtissue morphogenesis is becoming increasingly evident, however little is known abouthow these inputs shape and regulate gastrulation. Among the most well-knowntranscriptional activators that cells use to interpret mechanical signals are YAP proteins,yet their role in gastrulation remains elusive. Our detailed analysis of yap1 and yap1bdouble mutants in medaka fish shows that these mechanosensors are required for theassembly of the primary embryo axis: a key event for the establishment of thevertebrate body plan. Using quantitative imaging and live-sensors, we show that Yapactivity is required for the proper migration of dorsally converging cells towards theembryo midline. Thus, mutant cells display reduced velocity and migratory persistenceresulting in shorter cell displacements in many cases insufficient to reach the midline.Combining RNA-seq with previous DamID-seq data, we characterize the transcriptionalprogram directly activated by Yap proteins, which mostly entails the recruitment of actincytoskeleton regulators, ECM molecules and focal adhesion components. Moreover, weshow that Yap activation depends itself on intracellular tension, closing a positivefeedback loop that maintains directed cell migration.
%K Gastrulación
%K Desarrollo embrionario
%K Desarrollo animal
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