CABD study reveals new molecular mechanisms behind organ formation

A study, recently published in the journal 'Embo Journal', reveals, for the first time, the mechanisms that regulate basal folding, fundamental for the correct formation of organs.
 
This work, led by CABD researchers, highlights the importance of the study of these mechanisms, increasing the knowledge about developmental malformations.

The research group led by María Dolores (Lola) Martín Bermudo, a researcher at the Andalusian Center for Developmental Biology (CABD), a joint center of the Spanish National Research Council (CSIC), the Pablo de Olavide University (UPO) and the Andalusian Regional Government, in collaboration with the University College of London, has studied the molecular mechanisms that are crucial for the correct formation of tissues.

Each organ of any living being has a shape and structure necessary for the correct performance of its functions.  In fact, a malformation of any organ during embryonic development prevents its correct functioning. A key process is the folding of tissues, which, in addition to allowing the embryo to pass from a flat trilaminar embryo to a cylindrical shape in very early stages, is regularly used to shape the different organs.

In this work, in which the epithelium of the wing primordium of the fruit fly has been used as a study model, the molecular and cellular mechanisms that direct tissue folding have been discovered. These mechanisms are what allow organs to acquire their characteristic shape and, therefore, correct functionality.

However, although both types of folding occur during embryogenesis, little is known about the mechanisms that regulate basal folding. During apical folding, the actomyosin cytoskeleton of the cells, a contraction-producing machinery, pulls on the cadherin-mediated cell-cell adhesions, causing a reduction of their apical surfaces, resulting in a change of shape from cuboidal to trapezoidal, thus inducing apical folding. Until now, it was thought that in the basal part the process would be initiated in a similar way, where the actomyosin cytoskeleton would in this case pull the integrin-mediated adhesions between the cells and the basement membrane.



The authors: Andrea Valencia-Expósito and Lola Martín Bermudo

However, this work demonstrates that basal folding is initiated by a decrease in cell adhesion to the basement membrane. This triggers a shift of the apical adhesion module toward the basal side, where it replaces the basal module, leading to a contraction of the basal surface, which induces the shape changes necessary to induce basal folding. “These results show that the apical and basal adhesion modules play very different roles during epithelial folding, and while the apical module favors folding, the basal module inhibits it,” says first author Andrea Valencia-Expósito (CABD).

It is crucial to understand, both at the cellular and tissue level, how the forces derived from the interactions between adhesion molecules and the actomyosin cytoskeleton produce changes in cell shapes that induce tissue folding. “This work reveals for the first time the mechanisms that regulate basal folding,” says the principal investigator of this study, Lola Martín Bermudo (CABD). It also opens the door to future studies investigating how the regions where the tissue folds are specified, since folding in the wrong place can lead to malformation.

This research actively contributes to the understanding of developmental malformations due to misfolding.

Reference:

Andrea Valencia-Expósito, Nargess Khalilgharibi, Ana Martínez-Abarca Millán, Yanlan Mao and Maria D. Martín-Bermudo Local weakening of cell-extracellular matrix adhesion triggers basal epithelial tissue folding Embo Journal

https://doi.org/10.1038/s44318-025-00384-6