Publication highlights

Organisms grow through the division of the cells that make up our bodies. As well as growth, cell division is also essential for different types of cells to decide what cell type they will become (from different neurons in our brains to the cells that line our guts). How cells divide therefore needs to be tightly controlled both in space (so that the daughter cells after division end up in the right place) and in time (so that daughter cells make the correct choice of what to become). To make this process even more complicated, each cell type is very different in terms of shape, behaviour etc…, so cell division must adapt to the needs of each tissue, an aspect of biology we know very little about. Researchers at the Crick have found a protein called Meru (called after the Bengali word for “polar”) that can tell a cell in which direction and when to divide. Meru is located at one of the poles of a cell type called the sensory organ precursor and allows this cell to orient itself in the tissue and to time its division just right to allow both daughter cells to create the right structure.

Researchers at the Crick and the UCL Cancer Institute have identified a genetic change which happens early in lung cancer development, that makes cancer cells divide abnormally and become harder to treat. They studied non-small cell lung cancer samples from the Cancer Research UK-funded TRACERx study, to investigate which genetic changes make two hallmarks of cancer, chromosomal instability and whole genome doubling, more likely. They identified that a gene called FAT1 was mutated in lung cancer cells with unstable chromosomes before they doubled their genomes. Cells with a complete loss of FAT1 couldn’t divide properly to produce two new cells. When FAT1 and another gene involved in cell size regulation called YAP1 were removed, the cancer cells no longer doubled their genomes. This suggests that drugs that block YAP1 could be particularly effective against cells with high levels of chromosomal instability.

In this paper, the researchers show that a key steroid hormone of the fruit fly Drosophila, Ecdysone, both initiates and stops cell growth, depending on its level in the circulation. Low level Ecdysone promotes cell growth by removing a default anti-growth role of its receptor, while high levels trigger instructions from genes that stop cells from growing. The researchers then show mathematically and with synthetic reporters that combinations of basic gene regulatory elements can replicate the dual activity of this hormone. They highlighted the concentration of nuclear hormone signalling needed for growth control, which could be of interest for further research into growth hormone signalling for therapeutic purposes.

During development, multicellular organisms undergo stereotypical patterns of tissue growth in space and time, but how this is orchestrated remains unclear, largely due to the difficulty of observing and quantitating this process in a living organism. The Tapon and Salbreux labs used live imaging and computational methods to quantitatively analyse developmental growth in the fruit fly adult abdominal epidermis. Abdominal growth is initiated by degradation of the basement membrane to which the epidermal progenitor cells are attached and is terminated by rapid exit from the cell cycle, rather than a gradual slowdown, as occurs in some other tissues. Different developing tissues can therefore achieve their final size using distinct growth termination strategies.