Peter K. Dearden. Laboratory for Evolution and Development, Genetics Otago and the National Research Centre for Growth and Development, University of Otago
To explain complex and difficult things it is always useful, to borrow a phrase from the great Sydney Brenner, to have a ‘Don’t Worry Hypothesis’. Any hypothesis that allows you to imagine a explanation for something complex helps you work out how it might work. My glib ‘don’t worry hypothesis’ for lots of things (including gravity and baldness) has always been ‘rubber bands’.
It now turns out that my hypothesis is not so glib, rubber bands really do play a role in one of my favorite things (doesn’t scan in the sound of music song but who cares!); embryos.
Earlier this year Monier et al published a paper showing that rubber bands play important roles in stopping cells mixing across an embryonic boundary.
Embryonic boundaries are important things, in the fruit-fly Drosophila melanogaster, the well studied process of segmentation leads to an initially un-patterned embryo being divided into segments. In the middle of each segment lies a boundary, called the parasegment boundary, which is a lineage restriction. Cells on one side of the boundary will not mix with cells on the other side. The cells are effectively isolated from each other, but go on dividing, never crossing this invisible line-in-the-sand. While we understand much about how gene expression leads from an un-patterned, undivided embryo to make such boundaries, we haven’t, until now, understood how the cells are kept apart. We do know that this boundary is vital for the patterning of the embryo, and the adult structures, of the fly.
Such boundaries are not limited to flies, many examples exists in animal development. In the development of our own nervous system, very similar boundaries form between the developing rhombomeres, or segments, of the brain.
So what are they? Monier and co show, using a classical genetic approach, that whatever keeps these cells apart in the fly requires an unconventional myosin gene. By imaging the parasegment boundaries very carefully, looking for such myosins, they find an actino-myosin cable, a thin rubber band of tough elastic proteins, that runs along each of the boundaries. As cells divide on each side of the boundary, this cable holds them back, like a line of police with their arms linked, pushing back at a protest march. The tension and elasticity in the cable seems to be enough to hold cells on either side apart even as they divide and jostle for position.
Monier prove this by doing a very cool experiment. Using a technique called Chromophore Assisted Laser Inactivation, they effectively cut the cable, using a tiny laser down the microscope, in live embryos. With the cable cut, the cells mix, and the boundary vanishes. The rubber band of the cable appears to be the only thing holding the cells apart. It now appears that such rubber bands or cables may also be present at rhombomere boundaries in our brains.
This remarkable explanation for such boundaries work reminds us that sometimes the silly ‘don’t worry hypothesis’ contains at least a grain of truth. Imagining how something might work is often the best way to begin on the scientific journey of understanding it.