Research on sea lampreys provides insights into vertebrate evolution, revealing similarities in stem cell gene networks with jawed vertebrates and explaining differences in jaw formation. Credit: T. Lawrence, Great Lakes Fisheries Commission
These invasive blood-sucking fish “may hold the key to understanding where we come from.”
One of two without a jaw vertebrateSea lampreys, which cause great harm to Midwestern fisheries, are also helping scientists understand the origins of two important stem cells that played key roles in vertebrate evolution.
Northwestern University Biologists have pinpointed when the gene network that controls these stem cells evolved, providing insight into why lampreys lack their lower jaws.
Two types of cells, pluripotent blastula cells (or embryonic stem cells) and neural crest cells, are both “pluripotent,” meaning they can become all other cell types in the body.
In the new paper, the researchers compared lamprey genes with those of the jawed aquatic frog Xenopus laevis. Using comparative transcriptomics, the study revealed strikingly similar pluripotency gene networks between jawless and jawed vertebrates, even at the level of transcript abundance of key regulators.
Differences in gene expression
But the researchers also found important differences. seedBlastula cells express a key stem cell regulator, the pou5 gene, which is not expressed in lamprey neural crest stem cells. Loss of this factor may have limited the ability of neural crest cells to form the cell types found in jawed vertebrates (animals with backbones) that make up the head and jaw skeleton.
The study was recently published in the journal Neurology. Natural ecology and evolution.
Comparing the biology of jawless and jawed vertebrates can provide researchers with insight into the evolutionary origins of characteristics that define vertebrates, including humans, how differences in gene expression influence key differences in body shape, and what the common ancestor of all vertebrates looked like.
“Lampreys may hold the key to understanding our origins,” said Carol LaBonne of Northwestern University, who led the study. “In evolutionary biology, if you want to understand where a trait comes from, you can’t look to more complex vertebrates that have been evolving independently for 500 million years. You have to go back to the most primitive versions of the animal type you’re studying, and that leads us to hagfish and lampreys, which are the last living examples of jawless vertebrates.”
An expert in developmental biology, Lavonne is Professor of Molecular Biosciences in the Weinberg College of Letters and Sciences. She holds the Erastus Otis Haven Professorship and holds a leadership position at the National Science Foundation’s (NSF) new Simons National Institute for Theoretical and Mathematical Biology.
Lavonne and her colleagues previously demonstrated that the developmental origin of neural crest cells is linked to the retention of gene regulatory networks that control the pluripotency of blastula stem cells. In the new study, they investigated the evolutionary origins of the connection between these two stem cell populations.
The Importance of Neural Crest Cells
“Neural crest stem cells are like evolutionary Lego sets,” Lavonne says, “They can become very different types of cells, like neurons and muscles, but what all these cell types have in common is a common developmental origin within the neural crest.”
Although blastocyst-stage embryonic stem cells rapidly lose pluripotency and become restricted to distinct cell types as the embryo develops, neural crest cells retain the molecular toolkit that controls pluripotency until later in development.
Lavonne’s team discovered a fully intact pluripotency network within lamprey blastula cells, stem cells whose role in jawless vertebrates has not yet been resolved, suggesting that blastula and neural crest stem cell populations in jawed and jawless vertebrates coevolved at the base of vertebrates.
First author Joshua York, a postdoctoral researcher at Northwestern University, observed that there are “more similarities than differences” between lampreys and Xenopus frogs.
“Most of the genes that control pluripotency are expressed in the lamprey neural crest, but these cells lost expression of one of these key genes, pou5,” York said. “Surprisingly, even though pou5 is not expressed in the lamprey neural crest, when we expressed it in frogs it was still able to promote neural crest formation, suggesting that this gene is part of an ancient pluripotency network that was present in our earliest vertebrate ancestors.”
The experiment also helped support the hypothesis that the gene was specifically lost in one particular organism and not a later development of jawed vertebrates.
“Another striking finding of this study is that even though these animals are separated in evolution by 500 million years, there are strict constraints on the expression levels of genes needed to promote pluripotency,” Lavonne said. “The big unanswered question is why.”
Reference: “Intersections between basally evolved vertebrate blastula and neural crest stem cells,” Joshua R. York, Anjali Rao, Paul B. Huber, Elizabeth N. Schock, Andrew Montequin, Sarah Rigney, Carol Lavon, July 26, 2024; Natural Ecology and Evolution.
DOI: 10.1038/s41559-024-02476-8
This paper is National Institutes of Health (grants R01GM116538 and F32DE029113), the NSF (grant 1764421), the Simons Foundation (grant SFARI 597491-RWC), and the Walder Foundation through the Life Sciences Research Foundation. This work is dedicated to the memory of Dr. Joseph Walder.
