Defining the different body areas is one of the most critical steps when a new life begins. This process starts at very early stages of development, with the set-up of the head-tail axis. At that moment, the embryo loses its symmetry: one end becomes responsible for developing the head and the opposite end, the tail. In some species, such as the fruit fly, this polarity is established even earlier, in the mother’s ovaries. But how does the developing egg get it right? 

About twenty years ago, scientists found the earliest evidence that cells surrounding the eggs of fruit flies signal their polarization. The nature of this signal has been scratching their heads since then. Now, a new study from the Instituto Gulbenkian de Ciência (IGC) puts an end to this mystery: this signal has a mechanical nature, triggered by alterations in cell contacts. This data is a game changer in our understanding of polarity, something “fundamental for all cells but that has thus far been understood as a biochemical process”, explains Ivo Telley, leader of the study and the Physics and Intracellular Organization group at the IGC. 

In this study, carried out in the scope of a prestigious grant from the Human Frontier Science Program, the team showed that the contact between the developing egg and the surrounding cells determines the differential localization of polarization factors. These factors, in turn, influence the movement of messenger RNA (mRNA) molecules inside the developing egg, leading to asymmetrical gene expression in different body areas later on. This polarization is the first step to define what will be on one side of the embryo and what will be on the other – the head and the tail. 

To reach these conclusions, the researchers developed a specialized microscope that allowed them to both observe the egg chambers where the eggs of the fruit flies mature and to manipulate them. Under the microscope, they noticed that the egg loses contact with the surrounding cells on its back in final phases of development. Following this, the location of the proteins inside of it changes. That is, proteins that were once excluded from the egg’s back region were found where cell-cell contact was lost. 

When they used a pipette to aspirate and pull the cells surrounding the egg, detaching them in earlier stages of development, researchers realized that proteins distributed differently than expected at that moment. This led them to conclude that cell-cell contact is necessary to keep some proteins out of the posterior region and to maintain others, guaranteeing the polarity of the developing egg. “This is a good example of how information in living organisms can also be transmitted mechanically, through cell contact”, Ivo Telley remarks. These differences in protein localization, in turn, allow important messengers to move in the right direction. When cells lose contact, these messengers find other solutions to get where they are needed, opening space for molecules that will build the eggshell to deposit. 

These conclusions, now published in the Journal of Cell Biology, “add a trend-setting piece of information to the puzzle around how invertebrates define their body axis”, highlights Ana Milas, PhD student at the IGC and first author of the paper. The team hopes the study will inspire the scientific community to study the details of this cell-cell contact and how it can affect the protein network. The authors have already come up with some possible explanations: this contact could alter protein binding sites within the developing egg cortex or the physical and chemical conditions close by, resulting in their redirection.