“Studying the developmental genetics of Nematostella is sort of like taking a time machine into the very distant past,” said Gibson. “Our work allows us to ask what life looked like long ago— hundreds of millions of years before the dinosaurs. How did ancient animals develop from egg to adult, and to what extent have the genetic mechanisms that guide embryonic development endured across millennia?”

Most contemporary animals, from insects to vertebrates, develop by forming a head-to-tail series of segments that assume distinct identities depending on their position. Within a given segment, there is a further axis of polarity that informs cells whether they are at the front or back of the segment. Collectively, this is referred to as segment polarization.

Shuonan He, Ph.D., a former predoctoral researcher from the Gibson Lab, uncovered genes involved during development of the sea anemone, Nematostella vectensis, that guide the formation of segments and others that direct segment polarity programs strikingly similar to organisms higher up the evolutionary tree of life, including humans.

“The significance is that the genetic instructions underlying the construction of extremely different animal body plans, for example, a sea anemone and a human, are incredibly similar,” said Gibson. “The genetic logic is largely the same.”

The new work builds upon a 2018 study published in Science from the Gibson Lab that showed that sea anemones have an internal bilateral symmetry early in development with eight radial segments. The study demonstrated that Hox genes—master development genes that are crucial for human development—act to delineate boundaries between segments and likely had an ancient role in segment construction.

The team’s latest finding explores how segments form and what accounts for differences in their identities. Using spatial transcriptomics, or the differences in gene expression between segments, the team discovered hundreds of new segment-specific genes. These include two crucial genes that encode transcription factors that govern segment polarization under the control of Hox genes and are required for the proper placement of sea anemone muscles.

The astonishing diversity of organisms on Earth can be compared to the assembly of Legos. “Whether you construct a dinosaur, a sea anemone, or a human, many of the core genetic building blocks are largely the same despite drastically different animal forms,” said Gibson.

This is the first time that scientists have evidence of a molecular basis for segment polarization in a pre-bilaterian animal. While extensively studied in bilateral species like fruit flies and humans, the idea that cnidarian animals possess segmentation was unexpected. Now, the team has evidence that these segments are also polarized.

“This provides further evidence that investigating a broad diversity of animals can have direct implications for understanding general principles, including those which apply to human biology,” said Gibson. “Going one step further, by understanding the logic of sea anemone development and comparing it to what we see in vertebrates, we can also extrapolate back in time to understand how animals likely developed hundreds of millions of years ago.”

Additional authors include Wanqing Shao, Ph.D., Shiyuan Chen, Ph.D., and Ting Wang, Ph.D.

This work was funded by the National Institutes of Health (NIH) (award: RO1HG007175, award: U24ES026699, award: U01CA200060, award: U01HG009391, award: U41HG010972) and institutional support from the Stowers Institute for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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