WNTing to Know: Genome Editing at National Xenopus Resource Spurs New Work
Seven years ago, Marko Horb and Douglas Houston began dreaming up a project to demystify a long-standing question: How does the first body axis emerge in the developing frog embryo? Their patience, as Horb and colleagues bred mutant frogs specific to their research question -- and their persistence to keep experimenting during the 2020 pandemic shutdown -- paid off this fall, when they published their results in the journal Development.
“We knew it would take a long time, but a project can never be finished if it’s not started,” Horb said in an interview published as a companion to the research report.
It was fortuitous that in the same year (2015) Horb, an MBL Senior Scientist and Director of the National Xenopus Resource (NXR) at MBL, had received a grant to use CRISPR-Cas9 genome editing to make germline mutant frogs for the research community. For the collaboration with Houston, Professor of Biology at University of Iowa, the NXR generated females that lacked the gene Wnt11b, which was thought to be involved in axis formation. Over the next few years, they made several surprising discoveries about the activity of Wnt11b that illuminated why its presence in maternal frogs permits the first body axis (dorsoventral) to form, and the embryo to differentiate into the three germ layers that generate the tissues and organs of a new frog.
Today, the National Xenopus Resource has over 200 different frog mutants at various stages of development. Horb has also secured an R24 grant (Xenopus Mutant Resource) from the NIH’s Office of Research Infrastructure Programs to house visiting researchers who come to the MBL to work with the NXR’s resources.
Read more about this recent NXR collaboration and paper here:
Interview: “The People Behind the Papers: Douglas Houston and Marko Horb,” Development (2022), DOI: 10.1242/dev.201215
Lay summary: “WNTing to Break Symmetry”, Development (2022) 149 (17): e149_e1705.
Research Paper: Douglas W. Houston, Karen L. Elliott, Kelsey Coppenrath, Marcin Wlizla, Marko E. Horb (2022) Maternal Wnt11b regulates cortical rotation during Xenopus axis formation: analysis of maternal-effect wnt11b mutants. Development, DOI: 10.1242/dev.200552
