Discovery of cellular mechanisms that direct the folding of epithelia by which organs are formed

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Like origami, tissues are folded to give shape to organs or appendages / Alonso
Like origami, tissues are folded to give shape to organs or appendages / Alonso Rodríguez

A study by the Autonomous University of Madrid and CSIC demonstrates the role of cell proliferation and an intercellular communication mechanism in the formation of organisms. The research team validated the results with a mathematical model that predicts epithelial shape and cell behavior.

A research group at the Centro de Biología Molecular Severo Ochoa (CBM-CSIC-UAM), a joint center of the CSIC and the Universidad Autónoma de Madrid (UAM), has described the cellular mechanisms that contribute to the folding of tissues to give our organs their characteristic shape. Similar to the modeling of paper figures (origami), the folding of epithelia requires genetic instructions that determine in which specific areas these folds are to be produced. It is also necessary to generate mechanical compressive forces that help the epithelium to fold. The work is published in the journal Development.

To understand how these two processes -genetic instructions and the generation of mechanical compression forces- are coordinated to give rise to the characteristic shape of the organs, the laboratory of Carlos Estella, the CBM-CSIC-UAM researcher leading the work, has used the formation of the leg of the fly Drosophila melanogaster as a model. Drosophila is one of the most powerful organisms for modeling biological processes and human diseases due to its biological similarity to mammals.

The Drosophila leg is formed from a flat epithelium called the imaginal disc, which during metamorphosis gives rise to the adult fly leg. This tissue has to fold in a very specific way to give rise to the different segments of the limb that will allow its mobility. "The results obtained by our team show that cell proliferation generates compressive forces that contribute to tissue folding. In turn, the Notch signaling pathway, an intercellular communication mechanism used by organisms to determine the function and specific fate of complex structures during their formation, plays a critical role in the location of these epithelial folds," explains Estella.

"It is important to study both local and whole-tissue mechanisms that, combined, coordinate epithelial fold formation and organ architecture in a reproducible pattern," concludes the CBM-CSIC-UAM researcher.

The results of this study have been validated with a mathematical model that predicts epithelial shape and cell behavior after reducing cell proliferation and in the absence of Notch.

Bibliographic reference:

Rodríguez A., Foronda D., Córdoba S., Felipe-Cordero D., Baonza A., Miguez D. G., Estella C. Cell proliferation and Notch signaling coordinate the formation of epithelial folds in the Drosophila leg. Development. DOI: 10.1242/dev.202384.

More scientific culture in UAM Gazette.