Blog

These invasive, blood-sucking fish “may hold the key to understanding where we came from.”

One of the two Jawless vertebratessea ​​lampreys, which cause significant damage to fisheries in the Midwest, are also helping scientists understand the origin of two important stem cells that have played a key role in vertebrate evolution.

Northwestern University biologists have determined when the gene network that regulates these stem cells may have evolved and gained insight into what may be responsible for lampreys’ missing mandibles.

The two cell types—pluripotent blast cells (or embryonic stem cells) and neural crest cells—are both “pluripotent,” meaning they can become all the other types of cells in the body.

In a new paper, researchers compared the lamprey’s genes with those of Xenopus, a jawed water frog. Using comparative transcriptomics, the study revealed a strikingly similar pluripotency gene network in jawless and jawless vertebrates, even at the level of transcript abundance for key regulatory factors.

Differences in gene expression

But the researchers also found a key difference. While both kindsblastula cells express the gene pou5, a key regulator of stem cells, the gene is not expressed in neural crest stem cells in lampreys. The loss of this factor may have limited the ability of neural crest cells to form the types of cells found in jawed vertebrates (spiny animals) that build the head and jaw skeleton.

The study was recently published in the journal Natural ecology and evolution.

By comparing the biology of jawless and jawed vertebrates, researchers can gain insight into the evolutionary origins of traits that define vertebrates, including humans, how differences in gene expression contribute to key differences in body plan, and what the common ancestor of all vertebrates like.

“The lampreys may hold the key to understanding where we came from,” said Carol LaBonne of Northwestern, who led the study. “In evolutionary biology, if you want to understand where a feature came from, you can’t expect more complex vertebrates that have evolved independently over 500 million years. You have to look back to whatever the most primitive version of the type of animal you’re studying is, which takes us back to the anglerfish 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 National Institute for Theory and Mathematics in Biology.

LaBonne and her colleagues previously demonstrated that the developmental origin of neural crest cells is linked to the conservation of the gene regulatory network that controls pluripotency in blastula stem cells. In the new study, they investigated the evolutionary origins of the connections between these two populations of stem cells.

Importance of neural crest cells

“Neural crest stem cells are like an evolutionary Lego set,” LaBon said. “They become wildly different cell types, including neurons and muscles, and what all 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 restricted to different cell types relatively quickly as the embryo develops, neural crest cells hold onto the molecular toolkit that controls pluripotency later in development.

LaBonne’s team found a fully intact pluripotency network in lamprey blastula cells, stem cells whose role in jawless vertebrates has been an open question. This suggests that the blastula and neural crest stem cell populations of jawed and jawless vertebrates co-evolved at the vertebrate base.

Northwestern postdoctoral fellow and first author Joshua York observed “more similarities than differences” between the lamprey and Xenopus.

“While most of the genes controlling pluripotency are expressed in the lamprey neural crest, the expression of one of these key genes — pou5 — was lost in these cells,” York said. “Surprisingly, although pou5 is not expressed in the lamprey neural crest, it can promote neural crest formation when we express it in frogs, suggesting that this gene is part of an ancient pluripotency network that was present in our earliest vertebrate ancestors.”

The experiment also helped them hypothesize that the gene was lost specifically in certain creatures, rather than the jawed vertebrates that evolved later.

“Another remarkable finding of the study is that even though these animals are separated by 500 million years of evolution, there are strict limits on the levels of gene expression required to promote pluripotency,” LaBon said. “The big unanswered question is why?”

Reference: “Shared features of blastula and neural crest stem cells evolved at the base of vertebrates” by Joshua R. York, Anjali Rao, Paul B. Huber, Elizabeth N. Schock, Andrew Montequin, Sarah Rigney, and Carol LaBonne, July 26 2024, Natural ecology and evolution.
DOI: 10.1038/s41559-024-02476-8

The newspaper is funded by National Institutes of Health (grants R01GM116538 and F32DE029113), NSF (grant 1764421), the Simons Foundation (grant SFARI 597491-RWC), and the Walder Foundation through the Life Science Research Foundation. The study is dedicated to the memory of Dr. Joseph Walder.