Gene regulation and morphogenesis

Morphogenesis and mechanosensitive gene regulation


How is the formation of an organ so amazingly robust and reproducible? This perfection requires the coordination of multiple inputs, such as tissue mechanics, cellular geometries and gene regulatory mechanisms. However, how such diverse inputs are integrated and what sort of memory do the cells emply to propagate the mechanical and morphogenetic changes, remain poorly understood. In our group, we aim to understand how mechanical forces of the environment are translated into different morphogenetic events, such as cellular and nuclear states, and thus into gene-regulatory signals that will impact on cell identity, shape and proportionate patterning of the organ (scaling). Of particular interest for our group are the YAP and Wnt pathway - proteins that translate mechanical cues into biochemical processes incluidng changes in transcriptional states. We will first use these proteins as a hallmarck to study how different nuclear geometries and mechanical constrains of the substrate impact on the global cellullar epigenome defined by a set of mechanosensitive gene-regulatory regions (mGRRs).   

To answer these questions we use the development of the zebrafish eye and somites as a paradigm of organ formation. 

Once we unravel the set of mechanosensitive gene-regulatory mechanisms (mGRRs) that govern eye and somites formation in vivo, we will compare in vivo (embryos) with in vitro (organoids) to study the conservation of the mechanosensing cellular apparatus and the differential usage of these mGRRs upon mechanical perturbations. Integrative analysis will allow us to determine the in vitro growing conditions that better mimic the in vivo organ, not only at the morphological but also at the epigenetic level.  

We are also interested in understanding the coordination between patterning and organ size. This mechanism will guarantee that the different fractions of the organ are present in a proportional manner with respect to the final size of the organ, and of the organism. We will evaluate scale-invariant models to identify the molecular mechanisms that not only pattern the eye, but also do so in a proportionated way.

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