Invasive blood-sucking fish ‘may hold key to understanding where we came from,’ biologists say

The sea lamprey, one of only two jawless vertebrates that wreaks havoc on Midwestern fisheries, is simultaneously helping scientists understand the origins of two important stem cells that led to the evolution of vertebrates.

Biologists at Northwestern University have identified when the genetic network that regulates these stem cells may have evolved and have thus been able to better understand what might be responsible for the absence of mandibles in lampreys.

Both types of cells – pluripotent blastula cells (or embryonic stem cells) and neural crest cells – are both “pluripotent,” meaning they can become every other type of cell in the body.

In a new study, researchers compared genes from the lamprey to those from Xenopus, a jawed aquatic frog. Using comparative transcriptomics, the study revealed a surprisingly similar pluripotency gene network in jawless and jawed vertebrates, even down to the abundance of transcripts for key regulatory factors.

But the researchers also found a key difference. While blastula cells from both species express the gene pou5, a key regulator of stem cells, this gene is not expressed in the lamprey neural crest stem cells. The loss of this factor may have limited the ability of the neural crest cells to form the types of cells found in jawed vertebrates (animals with spines) that make up the skeleton of the head and jaw.

The study was published July 26 in the journal Nature Ecology & Evolution.

By comparing the biology of jawless and jawed vertebrates, researchers can better understand the evolutionary origins of the characteristics that define vertebrate animals, including humans, how differences in gene expression contribute to key differences in body plan, and what the common ancestor of all vertebrates looked like.

“Lampreys may hold the key to understanding where we come from,” said Northwestern’s Carole LaBonne, who led the study.

“In evolutionary biology, if you want to understand the origin of a feature, you can’t expect more complex vertebrates that evolved independently for 500 million years. You have to go back to the most primitive version of the type of animal you’re studying, which brings us back to the hagfish and the lamprey, the last living examples of jawless vertebrates.”

An expert in developmental biology, LaBonne is a professor of molecular biosciences in the Weinberg College of Arts and Sciences. She holds the Erastus Otis Haven Chair and is part of the leadership of the National Science Foundation’s (NSF) new Simons National Institute for Theory and Mathematics in Biology.

LaBonne and his colleagues have previously shown that the developmental origin of neural crest cells is linked to the maintenance of the genetic regulatory network that controls pluripotency in blastula stem cells. In the new study, they explored the evolutionary origin of the links between these two stem cell populations.

“Neural crest stem cells are like an evolutionary Lego set,” LaBonne said. “They become vastly different cell types, including neurons and muscles, and what all of these cell types have in common is a shared developmental origin within the neural crest.”

While embryonic stem cells at the blastula stage lose their pluripotency and become confined to distinct cell types relatively quickly as the embryo develops, neural crest cells retain the molecular toolkit that controls pluripotency later in development.

LaBonne’s team discovered a completely intact pluripotency network in lamprey blastula cells, stem cells whose role in jawless vertebrates had previously been an open question. This implies that blastula and neural crest stem cell populations from jawed and jawless vertebrates co-evolved at the base of vertebrates.

Joshua York, a postdoctoral researcher and first author at Northwestern, observed “more similarities than differences” between the lamprey and the Xenopus.

“While most of the genes controlling pluripotency are expressed in the lamprey neural crest, expression of one of these key genes, pou5, was lost in these cells,” York said.

“Surprisingly, even though the pou5 gene is not expressed in the neural crest of a lamprey, it could promote neural crest formation when we expressed it in frogs, suggesting that this gene is part of an ancient pluripotency network that was present in our early vertebrate ancestors.”

The experiment also helped them hypothesize that the gene had been specifically lost in certain creatures, and not something that jawed vertebrates developed later.

“Another remarkable finding of the study is that even though these animals are separated by 500 million years of evolution, there are tight constraints on the levels of gene expression needed to promote pluripotency,” LaBonne said. “The big unanswered question is: Why?”