Where do our limbs come from?

Date:
May 24, 2023
Source:
University of Colorado Anschutz Medical Campus
Summary:
Scientists have uncovered new clues about the origin of paired
appendages -- a major evolutionary step that remains unresolved
and highly debated.


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FULL STORY ==========================================================================
An international collaboration that includes scientists from the
University of Colorado School of Medicine has uncovered new clues about
the origin of paired appendages -- a major evolutionary step that remains unresolved and highly debated.

The researchers describe their study in an article published today in
the journal Nature.

"This has become a topic that comes with bit of controversy, but it's
really a very fundamental question in evolutionary biology: Where do our
limbs come from?" says co-corresponding author Christian Mosimann, PhD, associate professor and Johnson Chair in the Department of Pediatrics,
Section of Developmental Biology at CU School of Medicine.

That question -- where do our limbs come from? -- has been subject of
debate for more than 100 years. In 1878, German scientist Carl Gegenbaur proposed that paired fins derived from a source called the gill arch,
which are bony loops present in fish to support their gills. Other
scientists favor the lateral fin fold hypothesis, concluding that lateral
fins on the top and bottom of the fish are the source of paired fins.

"It is a highly active research topic because it's been an intellectual challenge for such a long time," Mosimann says. "Many big labs
have studied the various aspects of how our limbs develop and have
evolved." Among those labs are Dr. Mosimann's colleagues and co-authors,
Tom Carney, PhD, and his team at the Lee Kong Chian School of Medicine
at Nanyang Technological University in Singapore.

Chasing the odd cells For Mosimann, the inquiry into where limbs come
from is an offshoot of other research conducted by his laboratory on the
CU Anschutz Medical Campus. In his laboratory, his team uses zebrafish
as a model to understand the development from cells to organs. He and
his team study how cells decide their fate, looking for explanations
for how development can go awry leading to congenital anomalies, in
particular cardiovascular and connective tissue diseases.

Along the way, Mosimann and his lab team observed how a peculiar cell
type with features of connective tissue cells, so-called fibroblasts that
share a developmental origin with the cardiovascular system, migrated
into specific developing fins of the zebrafish. It turns out that these
cells may support a connection between the competing theories of paired appendage evolution.

"We always knew these cells were odd," he says. "There were these
fibroblast- looking cells that went into the so-called ventral fin, the
fin at the belly of the developing zebrafish. Similar fibroblast cells
didn't crawl into any other fin except the pectoral fin, which are the equivalent of our arms. So we kept noticing these peculiar fibroblasts,
and we could never make sense of what these were for many years."
The Mosimann lab has developed several techniques to track cell fates
during development in pursuit of their main topic, which is an improved understanding of how the embryonic cell layer, called the lateral plate mesoderm, contributes to diverse organs. The lateral plate mesoderm is
the developmental origin of the heart, blood vessels, kidneys, connective tissue, as well as major parts of limbs.

The paired fins that form the equivalent of our arms and legs are
seeded by cells from the lateral plate mesoderm, while other fins are
not. Understanding how these particular fins became more limb-like has
been at the core of a long- standing debate.

Developing new theories Hannah Moran, who is pursuing her PhD in the Cell Biology, Stem Cells and Development program in the Mosimann lab, adapted a method of tracking lateral plate mesoderm cells that contribute to heart development so that researchers could track the peculiar fibroblasts
related to limb development.

"My primary research project focuses on the development of the heart
rather than limb development," Moran says, "but there was a genetic
technique that I had adapted to map early heart cells, and so we were
able to implement that into mapping where the mysterious cells of the
ventral fin came from. And turns out, they are also from the lateral plate mesoderm." This crucial discovery provides a new puzzle piece to the big picture of how we evolved our arms and legs. Increasing evidence supports
a hypothesis of paired appendage evolution called the dual origin theory.

"Our data fit nicely into this combined theory, but it can also stand
on its own with the lateral fin theory," says Robert Lalonde, PhD,
postdoctoral fellow in the Mosimann lab. "While paired appendages arise
from the lateral plate mesoderm, that does not rule out an ancient
connection to unpaired, lateral fins." By observing the mechanisms of embryonic development and comparing the anatomy of existing species,
research groups like Mosimann's can develop theories on how embryonic structures may have evolved or have been modified over time.

"The embryo has features that are still ancient remnants that they have
not lost yet, which provides insight into how animals have evolved,"
Mosimann says.

"We can use the embryo to learn more about features that just persist
today, allowing us to kind of travel back in time," Mosimann says. "We see
that the body has a fundamental, inherent propensity to form bilateral, two-sided structures. Our study provides a molecular and genetic puzzle
piece to resolve how we came to have limbs. It adds to this 100-plus
year discussion, but now we have molecular insights." International collaboration Collaborations with colleagues in laboratories across
the country and around the world are another important part of the
study. Those scientists bring additional specializations and contribute
data from other models, including paddlefish, African clawed frogs,
and a variant of split-tail goldfish called Ranchu, to study embryonic development.

"There are labs on this on this paper that work on musculoskeletal
diseases, toxicology, fibrosis. We work on cardiovascular, congenital anomalies, cardiopulmonary anomalies, limb development, all related to
our interest on the lateral plate mesoderm," says Mosimann. "And then
together, you get to make such fundamental discoveries. And that's where
team science enables us to do something that is more than just the sum
of the parts." For all the considerable work and significance of the
study, the Mosimann team recognizes that it is a key step, but not the
end of the journey in the debate about paired appendages.

"I wouldn't say we've solved the question, or even disproven either
existing theory," says Lalonde. "Rather, we've contributed meaningful
data towards answering a major evolutionary question."
* RELATED_TOPICS
o Health_&_Medicine
# Stem_Cells # Immune_System # Pregnancy_and_Childbirth
o Plants_&_Animals
# Developmental_Biology # Biology # Biotechnology
o Fossils_&_Ruins
# Charles_Darwin # Evolution # Origin_of_Life
* RELATED_TERMS
o Recent_single-origin_hypothesis o Natural_selection o
Smallpox o Convergent_evolution o Evolutionary_psychology
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Timeline_of_human_evolution

========================================================================== Story Source: Materials provided by University_of_Colorado_Anschutz_Medical_Campus. Original written by Mark
Couch. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Keh-Weei Tzung, Robert L. Lalonde, Karin D. Prummel, Harsha
Mahabaleshwar, Hannah R. Moran, Jan Stundl, Amanda N. Cass, Yao
Le, Robert Lea, Karel Dorey, Monika J. Tomecka, Changqing Zhang,
Eline C.

Brombacher, William T. White, Henry H. Roehl, Frank J. Tulenko,
Christoph Winkler, Peter D. Currie, Enrique Amaya, Marcus C. Davis,
Marianne E.

Bronner, Christian Mosimann, Tom J. Carney. A median fin
derived from the lateral plate mesoderm and the origin of paired
fins. Nature, 2023; DOI: 10.1038/s41586-023-06100-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/05/230524181858.htm

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