A group of researchers from the Barcelona Institute of Molecular Biology, an organisation affiliated to the Higher Council for Scientific Research (IBMB-CSIC) and based at the Barcelona Science Park, has developed a method that permits to observe and manipulate cell growth and cell division in a living organism, the Drosophila fly, during one is its development stages. This new methodology has made it possible to identify several signalling pathways that control the coordination between these two processes. The study provides further insight into the internal rationale followed by these mechanisms and extends current knowledge on how these mechanisms function in many other situations of normal and abnormal development, such as in cancer. The study has been published today in the journal PLoS Biology (doi: 10.1371/journal.pbio.1000079) has been authored by Enrique Martín Blanco, Nikolay Ninov and Cristina Manjon.

”

One of the fundamental issues that remains unsolved in the field of molecular biology is to ascertain what coordinates cell growth and division during development; that is, to determine what sort of signals tell a cell to start or stop growing or to interrupt its division process. These two complementary processes have been extensively studies in cell cultures. However, how they work “in vivo” on a living organism is still not well known.

Researchers at IBMB-CSIC have developed a method that allows the observation and manipulation of cell growth and division in the Drosophila fly during formation of its abdominal epithelium. Thanks to this methodology that combines high-resolution non-invasive microscopy and genetic recombination, the authors have identified several signalling pathways that govern the coordination between these two processes: the PI-3-kinase enzyme, the ecdysone (major hormone in insect molting or ecdysis) and the EGF.

As observed by the researchers, activation of PI-3-kinase triggers cell growth. When cells reach a certain size, the ecdysone is activated and the cells stop to grow to start dividing. Whilst undergoing division, the cells get progressively smaller in size to a point where the division gets to a minimum and then without stopping to divide, the cells start to grow bigger in size again. At this stage, two simultaneous cascades are necessary: PI-3-and the EGF growth factor.

With the incorporation of mutant cells devoided of the receptor of any of these three signalling pathways (factor EGFR, PI-3-kinase or ecdysone) it has been possible to demonstrate that these pathways are responsible for signaling and activating each of the process stages. This has allowed researchers to see that cells, in which the ecdysone receptor does not work, do not undergo division when they have to.

This discovery is of most importance in order to gain a better understanding of the basic mechanisms that regulate cell growth and division, both in normal as well as in abnormal conditions, such as in cancer. It is known, for instance, that in multiple cases, the proliferation of cancerigenous cells is associated with hormone responses or with permanent activation of PI-3-kinase or EGF routes, which as demonstrated in the work herein mentioned, signal the start and progression of cell division during development.