This nightmarish creature that one might attribute to Hieronymus Bosch is actually a metamorphosing sea-urchin larva about two millimeters in size. The embryonic skeleton of thin rods in the larva’s arms remain, while adult skeletal elements—spines, plates, and tube foot disks—have already appeared.

Building a Sea Urchin, One Cell at a Time

“Cats beget cats and frogs beget frogs, so how you develop depends on what genome you’ve inherited,” says Eric Davidson, the Chandler Professor of Cell Biology at Caltech. Now, for the first time ever, Davidson’s lab has mapped in its entirety the complex network of genes responsible for creating a specific cell—a skeletal cell, in this case, not in a cat or a frog but in a sea urchin.

Genes, of course, are the assembly instructions for creating an organism, and in 2006, the Baylor College of Medicine Human Genome Sequencing Center, along with Caltech’s Davidson and Senior Research Associate in Biology Andy Cameron, plus researchers from more than 70 other institutions, published the entire 814-million-letter instruction book for the California purple sea urchin (Strongylocentrotus purpuratus). This genome, as it’s called, is about one-fourth the size of the human genome and contains some 23,300 genes.

That was the easy part. The challenge now is to tease out the relationships between these genes—how they turn one another on and off at specific times in the embryo’s development to create the panoply of adult cell types.

Davidson’s team focused on a cell line that takes in minerals from seawater to build skeletal rods. The gene regulatory network that drives this process can be thought of as a blueprint, but unlike a regular blueprint, which describes how static pieces of a structure fit together, the gene regulatory network is a dynamically changing plan, with the relationships between genes at one stage providing the basis for the next stage. The work, coauthored by postdoc Qiang Tu and Paola Oliveri, now of University College London, appeared in the April 22 issue of the Proceedings of the National Academy of Sciences.

Says Davidson, “We’ve reached the point where everything you see in a microscope for this cell lineage can be interpreted in terms of what we know about this control program. The network concerns only one day in the life cycle of an animal that lives for 50 or a hundred years, and only one cell lineage of the embryo, but it is a step forward to be able to relate the biology to the regulatory DNA sequence in this way.”

In a second paper in the same issue, Davidson and postdoc Feng Gao report that this regulatory network evolved from another skeletal-cell-forming network present in adult urchins. Sea urchins are the only echinoderms—which also include starfish, brittle stars, sea cucumbers, sand dollars, and other creatures—to have an embryonic skeleton made from this cell lineage as well as an adult one. By analyzing the gene regulatory network, Gao and Davidson were able to show that the embryonic skeleton arose because a substantial portion of the adult skeleton’s regulatory apparatus had been hijacked. This happened when the control systems for several genes at the top of the adult hierarchy got mutated in such a way as to come under the embryonic cell lineage’s control, at which point the entire downstream adult network became active in the embryonic lineage. The fossil record shows that this change happened some 250 million years ago. “Gene regulatory network redeployment is one way of introducing novelties into an animal’s body plan during evolution,” says Gao.

Davidson’s lab is pressing on to decipher the other gene regulatory networks, hoping to eventually crack the code for the whole embryo. “The evolution of animals is due to changes in the structure of these gene regulatory networks, so this work provides us with an opportunity to study evolution in a new and decisive way,” he says. —KS/DS