A Mechanical DNA Clock Determines Embryos’ Segmentation

Researchers have discovered a mechanism for how animal embryos segment themselves (roughly from head to tail) with extreme precision and consistent timing: the DNA responsible for determining the fate of different segments unravels in the same order and with the same timing as the segmentation itself. Remember that DNA is generally twisted and looped up as tightly as possible, so that molecules that could span 6 feet end-to-end are crammed up into a few nanometres; specific DNA sequences get unwound when they’re needed so that they can be read and transcribed by proteins, and then have an effect on the cell. 

From Science Daily:

During the development of an embryo, everything happens at a specific moment. In about 48 hours, it will grow from the top to the bottom, one slice at a time — scientists call this the embryo’s segmentation. “We’re made up of thirty-odd horizontal slices,” explains Denis Duboule, a professor at EPFL and Unige. “These slices correspond more or less to the number of vertebrae we have.”

Every hour and a half, a new segment is built. The genes corresponding to the cervical vertebrae, the thoracic vertebrae, the lumbar vertebrae and the tailbone become activated at exactly the right moment one after another… How do the genes know how to launch themselves into action in such a perfectly synchronized manner? “We assumed that the DNA played the role of a kind of clock. But we didn’t understand how.”

Very specific genes, known as “Hox,” are involved in this process. Responsible for the formation of limbs and the spinal column, they have a remarkable characteristic. “Hox genes are situated one exactly after the other on the DNA strand, in four groups. First the neck, then the thorax, then the lumbar, and so on,” explains Duboule. “This unique arrangement inevitably had to play a role.”

The process is astonishingly simple. In the embryo’s first moments, the Hox genes are dormant, packaged like a spool of wound yarn on the DNA. When the time is right, the strand begins to unwind. When the embryo begins to form the upper levels, the genes encoding the formation of cervical vertebrae come off the spool and become activated. Then it is the thoracic vertebrae’s turn, and so on down to the tailbone. The DNA strand acts a bit like an old-fashioned computer punchcard, delivering specific instructions as it progressively goes through the machine.

“A new gene comes out of the spool every ninety minutes, which corresponds to the time needed for a new layer of the embryo to be built,” explains Duboule. “It takes two days for the strand to completely unwind; this is the same time that’s needed for all the layers of the embryo to be completed.”

This system is the first “mechanical” clock ever discovered in genetics. And it explains why the system is so remarkably precise.

I wanted to share this article both because it seems like a very novel discovery and because it touches on some DNA and development fundamentals, but to be honest it’s a bit confusing to me, and I wish I could read the actual article in Science for an explanation. This article basically reads like the embryo is one cell with one set of DNA, which, unless I’m thoroughly off the mark, is not the case during segmentation, by which I’m assuming they mean somitogenesis. This begs the question: in which cells are they noticing this Hox activity? How is this pattern being communicated between cells? 

I may be missing something obvious, but I wish this Science Daily article were clearer. Anyway, in conclusion, here’s an interesting time-keeping mechanism during embryogenesis 🙂

Side note: Apologies for the gap in posts since Thursday; like I said in the previous post, I was marathon cramming for my GRE biochemistry test on Saturday, and my brain has been hibernating since then. It’s slowly recovering from the trauma. Fear not, though, we won’t miss a thing: I’ll be going through every article in my RSS feed since Thursday, all 1000+. No science will escape us!

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