An international team of researchers, including scientists from the University of Colorado School of Medicine, has discovered new information about the origin of paired appendages. This major evolutionary transition remains unresolved and hotly contested.

Carl Gegenbaur, a German scientist, hypothesized in 1878 that paired fins originated from the gill arch, bony loops seen in fish to support their gills. Other scientists believe that the concept of the lateral fin fold is correct.

Mosiman said, “It is a very active research topic because it has been an intellectual challenge for a long time. Many major laboratories have studied the various aspects of how our limbs develop and have evolved.”

To the collaborators and co-authors of Dr. Mosimann include Tom Carney, Ph.D., and his team at Lee Kong Chian School of Medicine at Nanyang Technological University.

Mosimann sees the research on where limbs come from as an extension of his group’s previous research at the CU Anschutz Medical Campus.

In his lab, his team uses zebrafish as a model to study the progression from cells to organs. He and his colleagues are investigating how cells choose their fate, seeking explanations for how development can go wrong, resulting in congenital malformations such as cardiovascular disease and connective tissue disease.

Mosimann and his team observed how a peculiar cell type with characteristics of connective tissue cells, called fibroblasts, migrated to specific developing zebrafish fins. This suggests that these cells may support a link between the competing theories of paired appendage evolution.

He said, “We always knew that these cells were foreign. There were those fibroblast-like cells that ended up in what’s called the ventral fin, the fin on the belly of the developing zebrafish. Similar fibroblast cells did not crawl into any other fin except the pectoral fin, which is the equivalent of our arms. So we kept noticing these peculiar fibroblasts, and for years we could never understand what these were.

The Mosimann lab has developed several techniques to track the fate of cells during development in view of their main topic: a better understanding of how the embryonic cell layer, the mesoderm of the lateral plate, contributes to diverse organs. The mesoderm of the lateral plate is the developmental origin of the heart, blood vessels, kidneys, connective tissue, and major parts of the limbs.

Hannah Moran, a Ph.D. student in the Mosimann lab’s cell biology, stem cells, and development program, changed a method for tracking lateral plate mesoderm cells that contribute to heart development so researchers could track the unusual fibroblasts associated with development of limbs.

said Moran, “My primary research project focuses on heart development rather than limb development, but there was a genetic technique that I adapted to map early heart cells, so we were able to implement that to map where the mysterious cells of the ventral fin came from. And it turns out that they are also from the mesoderm of the lateral plate.

This important discovery adds another piece to how we evolved our arms and legs. Increasing evidence supports the idea of ​​dual origin, a hypothesis of paired evolution of appendages.

“Our data fit nicely into this combined theory, but can also stand alone with the side fin theory.” adds postdoctoral fellow Robert Lalonde, Ph.D., of the Mosimann lab.

He said, “While paired appendages arise from the lateral plate mesoderm, that does not preclude an ancient connection with unpaired lateral fins.”

Mosimann’s research group can build theories about how embryonic structures may have evolved or changed over time by tracking embryonic developmental mechanisms and comparing the anatomy of current species.

Mosiman said, “The embryo has features that are still ancient relics that they haven’t lost yet, providing insight into how animals evolved.”

He added, “We can use the embryo to learn more about features that exist today, allowing us to travel back in time. The body has a fundamental, inherent tendency to form bilateral, two-sided structures. Our study provides a molecular and genetic puzzle piece to solve how we got limbs. It adds to this discussion of more than 100 years, but now we have molecular insights.”

Mosimann’s study provides a molecular and genetic puzzle piece to solve how we got limbs. International collaboration with colleagues in laboratories across the country and globally is also an important part of the research.

Mosiman said, “There are labs on this paper working on musculoskeletal disorders, toxicology, fibrosis. We are working on cardiovascular, congenital anomalies, cardiopulmonary anomalies and limb development, all related to our interest in the lateral plate mesoderm.”

The researcher said, “And together you make such fundamental discoveries. And that’s where team science allows us to do something more than just the sum of its parts.”

Collaborations with partners in laboratories across the country and around the world bring additional specialties and data from several models, such as paddlefish, African clawed frogs, and Ranchu, a split-tailed goldfish variety.

The Mosimann team realizes that this is an important step. However, there is more to the end of the argument about paired appendages. They have provided valuable information for answering a crucial evolutionary conundrum.

Lalonde said, “I wouldn’t say we’ve solved the question or disproved an existing theory. Rather, we’ve contributed meaningful data to answering an important evolutionary question.”