Gene linked to evolution of limb development identified

Date:
October 5, 2021
Source:
University of Kentucky
Summary:
A new study gives insight into how limb development evolved in
vertebrates. The findings identify a gene that plays a central
role in the evolution of limb development in vertebrates. By
manipulating this gene in mice, researchers were able to activate
an ancestral form of limb development seen in early tetrapods
(four-legged vertebrates).



FULL STORY ========================================================================== University of Kentucky College of Medicine researchers were part of a new
study that gives insight into how limb development evolved in vertebrates.


==========================================================================
The findings, published in Current Biology Oct. 4, identify a gene
that plays a central role in the evolution of limb development in
vertebrates. By manipulating this gene in mice, researchers were able to activate an ancestral form of limb development seen in early tetrapods (four-legged vertebrates).

In the limbs of all tetrapods, the bones on the hands and feet on the
outside edge form first, known as postaxial development. The study focuses
on salamanders, which are the only exception to this rule: their limb
bones develop preaxially, or from the inside edge; the thumb before pinky.

"For more than 100 years, scientists have wondered if preaxial
development evolved uniquely in salamanders," said study co-author
Randal Voss, Ph.D., University Research Professor in the Department of Neuroscience and Director of the Ambystoma Genetic Stock Center. "Now
we understand that it's ancestral to the postaxial mode seen in all
other tetrapods. Salamanders are not unusual, they simply retained the ancestral mechanism of vertebrate limb development." Voss, who studies salamanders' unique ability to regenerate body parts including limbs,
teamed up with principal investigator Susan Mackem, M.D., Ph.D., with the National Cancer Institute's Center for Cancer Research, whose research
focuses on the signaling networks involved in limb development.

In both mice and axolotl salamanders, researchers manipulated the function
of Gli3, a gene that is known to be important in regulating the pattern
of limb development. Mice with excess GLi3 repressor activity reverted
to preaxial limb development -- just like salamanders. Conversely, when
Gli3 was "knocked out" in salamanders, they developed limbs postaxially,
like the mice and all other tetrapods.

"In evolutionary terms, what we'd basically done in mice is bring back
the ancestral form of limb development by gene manipulation, proving
that Gli3 was key for the shift from preaxial development seen in early tetrapods," said Voss.

The results are significant to developmental and evolutionary biologists, including paleontologists that have recently identified fossils that
support the idea that preaxial limb development is the ancestral mode of
limb development in vertebrates. They also give insight on evolutionary questions about the transition from fins as vertebrates acquired limbs
and moved onto land.

In the future, findings from this work will also help answer questions
about limb regeneration, Voss says. Salamanders are one of the few
four-legged animals that can fully regenerate a limb after losing it
and scientists have proposed the capability is linked to their retained preaxial development.

Voss now plans to study limb regeneration in salamanders that his lab genetically manipulated for postaxial development.

========================================================================== Story Source: Materials provided by University_of_Kentucky. Original
written by Elizabeth Chapin. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Anna Trofka, Bau-Lin Huang, Jianjian Zhu, William F. Heinz, Valentin
Magidson, Yuki Shibata, Yun-Bo Shi, Basile Tarchini, H. Scott
Stadler, Mirindi Kabangu, Nour W. Al Haj Baddar, S. Randal Voss,
Susan Mackem.

Genetic basis for an evolutionary shift from ancestral preaxial
to postaxial limb polarity in non-urodele vertebrates. Current
Biology, 2021; DOI: 10.1016/j.cub.2021.09.010 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211005124828.htm

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