According to a new study, researchers observed during the development of an embryo, every single cell needs to know who it is, where it is, and what it must do. They have identified a gene that oversees the shape of the cell. To make a fully-grown organism in the right shape, the forms of many cells need to be changed in a coordinated way.

Only when the cell is polarized in the right way can it change the shape in exactly the way which is needed to form a certain structure or organ.

Good things take time — breakthrough after 20 years of research

The polarity of cells is controlled by a relatively small group of genes, which remained almost unchanged in all higher animals over millions of years. "Almost twenty years ago, my first PhD-student found an interesting, unnamed gene, which was likely participating in the polarity," says Prof. Andreas Wodarz from CECAD.

The first tests were promising even though the gene turned out to be very mutable. In the beginning, the gene seemed to code for a mid-sized protein of about 900 amino acids. By and by it became clear that the gene is much bigger and holds information for a protein almost twice the size.

Almost ten years later, another doctoral candidate, Hamze Beati, conducted experiments that provided first hints towards the functioning of the gene. The result was astonishing: The cells changed their form and contracted at the top. Observed from above, the cells looked significantly smaller, which resulted in the name for the gene: "smallish."

Gene products are stored in the egg cells

Irina Peek, doctoral student number three and co-first author of the publication, made the breakthrough in 2016. In smallish mutant embryos where the mother generation was already mutant and could not store proteins in the egg cell, shape generation was out of control.

"Smallish is important for the correct shape of the cells. In embryos completely missing smallish, we see that the cells are loose and do not have tension anymore," says Irina Peek. "Those cells are not able to perform coordinated cell shape changes, which are essential for shape generation."

"The gene is highly conserved across evolution, which means it can be found in similar ways in many organisms. The human homolog LMO7 is known as a tumor suppressor. In a range of tumors reduced amounts of LMO7 were shown, which indicates a function in the growth control of tumors,"

In Future, the researchers want to investigate how smallish interacts with other proteins, how it gets to the right place in the cell, and how it influences the shape. One thing is for sure: smallish will not be put back in the drawer anytime soon.