A central problem in developmental biology is to understand how initially identical cells can differentiate into the spatially ordered structures that form an adult organism. Traditionally, it has been assumed that cell differentiation is directed by external signals. However, the last decade of research has highlighted that cells can self-organize to form complex structures in the complete absence of external signals (Sheth and Marcon et al. Science 2012, Marcon and Sharpe Curr. Opin. Genet. Dev. 2012, Raspopovic and Marcon et al. Science 2014).
The main goal of our laboratory is to identify which mechanisms drive the formation of self-organizing dissipative structures in multicellular systems. To pursue this goal, we study how embryonic stem cells spheroids are able to spontaneously self-organize to specify the three germ layers and to undergo tissue movements that mimic early embryonic development. We do so by using a multidisciplinary systems biology approach that combines experiments, three dimensional imaging and modeling. On the theoretical side, we use multicellular simulations and mathematical analysis to identify which tissue movements (Marcon et al. Plos Comput. Biol. 2011) and gene regulatory networks (Marcon et al. eLife 2016) underlie self-organization. On the experimental side, we use 3D light sheet microscopy to capture the dynamics of germ layer self-organization in normal situations and upon perturbations of developmental signaling pathways. Our long-term goal is to develop a comprehensive computational model of germ layer patterning to explore how gene regulatory networks, cellular behaviors and external signals are coupled by feedback to control patterning and morphogenesis. This will allow us to devise novel bioengineering strategies to steer stem cell development towards normal embryonic development or towards the induction of specific cell fates for tissue-engineering.
Our laboratory is part of the Gene Expression and Morphogenesis Unit (GEM) at the Andalusian Centre for Developmental Biology (CABD), in Seville, where we work in close interaction with other groups that study Mouse, Zebrafish, Xenopus, Drosophila and Caenorhabditis development.
"It is by avoiding the rapid decay into the inert state of ‘equilibrium’ that an organism appears so enigmatic."