Sea lampreys, one of only two jawless vertebrates that are wreaking havoc on Midwest fisheries, are simultaneously helping scientists understand the origins of two key stem cells that drove vertebrate evolution.
Biologists at Northwestern University have pinpointed when the gene network that regulates these stem cells may have evolved, providing insight into what could be responsible for lampreys’ missing mandibles.
The two cell types – pluripotent blastula cells (or embryonic stem cells) and neural crest cells – are both ‘pluripotent’, meaning they can become any other cell types in the body.
In a new paper, researchers compared the lamprey’s genes with those of Xenopus, a jawed aquatic 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.
But the researchers also discovered an important difference. Although the blastula cells of both species express the pou5 gene, an important stem cell regulator, 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 cell types found in jawed vertebrates (animals with spines) that form the head and jaw skeleton.
The research will be published in the journal on July 26 Nature ecology and evolution.
By comparing the biology of jawless and jawless vertebrates, researchers can gain insight into the evolutionary origins of traits that define vertebrates, including humans, how differences in gene expression contribute to important body plan differences, and how the common ancestor of all vertebrates looked like. like it.
“Lampreys could be the key to understanding where we came from,” says Carole LaBonne of Northwestern, 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 evolved independently for 500 million years. You have to look back at the most primitive version of the type. of the animal you are studying, which leads us back to hagfish and lampreys – the last living examples of jawless vertebrates.
LaBonne is an expert in developmental biology and professor of molecular biosciences at 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 her colleagues previously showed that the developmental origins of neural crest cells were linked to the maintenance of the gene regulatory network that controls pluripotency in blastula stem cells. In the new study, they examined the evolutionary origins of the links between these two stem cell populations.
“Neural stem cells are like an evolutionary Lego set,” says LaBonne. “They become vastly different types of cells, 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 lose their pluripotency at the blastula stage and become restricted quite quickly to different cell types as an embryo develops, neural crest cells hold on to the molecular toolkit that controls pluripotency later in development.
LaBonne’s team found a fully intact pluripotency network within lamprey blastula cells, stem cells whose role within jawless vertebrates was an open question. This implies that blastula and neural stem cell populations of jawed and jawless vertebrates co-evolved at the base of vertebrates.
Northwestern postdoctoral fellow and first author Joshua York observed “more similarities than differences” between the lamprey and Xenopus.
“Although most of the genes that control pluripotency are expressed in the lamprey neural crest, expression of one of these key genes – pou5 – was lost in these cells,” York said. “Amazingly, even though pou5 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 earliest vertebrate ancestors.”
The experiment also helped them hypothesize that the gene was specifically lost in certain creatures, and not something that was later developed by jawed vertebrates.
“Another notable finding of the study is that even though these animals are separated by 500 million years of evolution, there are strict limits on the expression levels of genes necessary to promote pluripotency.” said LaBonne. “The big unanswered question is: why?”
The article was funded by the 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. The study is dedicated to the memory of Dr. Joseph Walder.
