Institute researchers create a detailed biological profile of the lives of a strange sea creature

Documenting the details of Botryllus’ sexual and asexual reproduction may give insight into the genetic programs regulating our own stem cells.

January 26, 2021

By Christopher Vaughan

Researchers at the Institute and Stanford’s Bio-x have compiled a thorough genetic and microscopic atlas of the developmental history of the unusual sea creature Botryllus schlosseri, which reproduces sexually during one part of its life, to make the chordate form in its life history,  and asexually as an invertebrate during another  part of its life. The researchers documented similarities and differences between the developmental programs guiding each form of reproduction and made surprising findings that may inform our understanding of how reproduction and regeneration occurs in all animals. 

“One can compare the reproduction and development of Botryllus after fertilization as parallel to our embryonic and fetal development, while its asexual reproduction and development is akin to the maintenance of our own tissues and organs throughout life with tissue-specific stem cells,” said Irv Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine. 

Botryllus is a creature with a very interesting life cycle. The sea-dwelling organism is the closest living invertebrate relative to humans, but it lives a very different life from us. Botryllus  goes through two distinct phases—In one phase it reproduces sexually to create a tadpole-like creature with two brains which direct the muscles in the tail to swim directionally. This creature swims around until it finds a nice bit of underwater real estate to latch onto,  settling down and absorbing one of its brains, its eye and its muscular tail, to begin an even stranger stage of life. In this phase, post-settlement, it begins reproducing asexually, budding off new individuals from the initial Botryllus. This budding process utilizes both tissue-specific stem cells as well as the germ stem cells.  

All members live  together communally in a colony that appear to be one organism. The tadpole-like creatures that swim out to find a new home mysteriously sense whether a compatiblility gene is shared or different, and co-settle if they share the gene. The individuals who live together and share a compatibility gene join together blood vessels that extend into the adjacent sibling. The individuals who live together and share the same variant of the compatibility gene called BHF,  join together blood vessels that extend into the adjacent sibling. If they don’t share this gene, the adjacent colony rejects the interloper and scars off the place where it tried to enter, blocking future immigrants. Between the colonies that share blood circulation and exchange cells, germline stem cells can colonize and take over the reproductive organs of other individuals in the colony. 

Institute researchers in the Weissman laboratory have long studied this strange sea creature because it offers the chance to answer fundamental questions about how stem cells are programmed to behave during development, how cells can identify whether other cells belong in the group or not  and how cells attack invaders. In a paper published this week in the journal Cell Reports, institute researchers reveal details of the  molecular/genetic and stem cell programs that guide reproduction in both the sexual and asexual phases of Botryllus’s life, along with the morphological changes that researchers can see under the microscope. 

“Many organisms, such as corals and sponges, can reproduce both asexually and sexually, but no one has compared these processes in the same organism in detail before,” said Ayelet Voskoboynik, PhD, a co-corresponding author on the paper. 

The researchers took samples during different stages of development when Botryllus reproduces sexually through embryogenesis, and when it reproduces by budding a new individual off the old one, a process called blastogenesis. The co-lead author, Mark Kowarsky, a grad student in the laboratory of Professor Stephen Quake, DPhil, from Bio-X, used bioinformatic methods to precisely analyze which genes were being expressed at which stages of both processes. 

“Despite only sharing 30 percent of the genes guiding the two developmental processes, we were surprised that organs develop in the same order and have the same timing for gene expression in specific tissues” said Mark .

“Convergent morphology need not imply convergent molecular mechanisms,” added Chiara Anselmi, PhD, one of the paper’s a co-lead authors.

Furthermore, many of the shared genes were for transcription factors, which turn on and off whole groups of genes. “What this means is that during embryogenesis and blastogenesis, the same transcription factors are promoting different sets of genes,” Voskoboynik says. 

Development of tissues in both embryogenesis and blastogenesis is governed by how those sets of genes are activated in tissue-specific stem cells, which may offer lessons for how gene programs in our own bodies change after we finish embryonic development and start using the same stem cells to regenerate and repair tissues in adulthood, the researchers say. 

Overall, the detailed analysis of very different forms of development is now a platform on which other research can ask far-flung scientific questions, Weissman says. “ For example, we have known since the 1970s that mate selection in vertebrates such as mice, dogs and humans has an olfactory component genetically linked to the MHC genes that define our immunological identity,” he said. “Now in Botryllus we might define the cellular and molecular principles that this is based on.”

Other Stanford scientists involved in the research are life science research professionals Karla Palmeri and Kathi Ishizuka.   

Link to Cell Reports