Aided by stem cells, a lizard regenerates a perfect tail for first time
in more than 250 million years
Experiment helps inform efforts to improve wound-healing in humans

Date:
October 14, 2021
Source:
University of Southern California
Summary:
Lizards can regrow severed tails, making them the closest relative
to humans that can regenerate a lost appendage. But in lieu of
the original tail that includes a spinal column and nerves, the
replacement structure is an imperfect cartilage tube. Now, a study
describes how stem cells can help lizards regenerate better tails.



FULL STORY ========================================================================== Lizards can regrow severed tails, making them the closest relative
to humans that can regenerate a lost appendage. But in lieu of the
original tail that includes a spinal column and nerves, the replacement structure is an imperfect cartilage tube. Now, for the first time,
a USC-led study in Nature Communications describes how stem cells can
help lizards regenerate better tails.


========================================================================== "This is one of the only cases where the regeneration of an appendage
has been significantly improved through stem cell-based therapy in
any reptile, bird or mammal, and it informs efforts to improve wound
healing in humans," said the study's corresponding author Thomas Lozito,
an assistant professor of orthopaedic surgery and stem cell biology and regenerative medicine at the Keck School of Medicine of USC.

These new and improved lizard tails exhibit what is known as "dorsoventral patterning" -- meaning they have skeletal and nerve tissue on the upper
or dorsal side, and cartilage tissue on the lower or ventral side.

"Lizards have been around for more than 250 million years, and in all
that time no lizard has ever regrown a tail with dorsoventral patterning,
until now," said Lozito. "My lab has created the first regenerated lizard
tails with patterned skeletons." To achieve this, the team of scientists
from the medical schools at USC and the University of Pittsburgh analyzed
how lizard tails form during adult regeneration, compared to embryonic development. In both cases, neural stem cells or NSCs -- the stem cells
that build the nervous system -- play a central role.

Adult NSCs produce a molecular signal that blocks skeletal and nerve
formation and encourages cartilage growth, effectively "ventralizing"
both sides of the tail. This results in the cartilage tube typical of regenerated tails.



==========================================================================
Even in the absence of this ventralizing signal, adult NSCs are incapable
of generating new nerve tissue for the dorsal side of the tail.

In contrast, embryonic NSCs produce this "ventralizing" signal only
in the cartilage region that becomes the lower or ventral side of the
tail. Meanwhile, in the absence of this signal, the upper or dorsal side develops skeletal and nerve tissue. Thus, the tail acquires the intricate dorsoventral patterning characteristic of original embryonic appendages.

However, if embryonic NSCs are implanted into adult tail stumps, they
respond to the ventralizing signal, and fail to develop into dorsal
structures.

To overcome these obstacles, Lozito's team used gene-editing tools
to make embryonic NSCs unresponsive to the ventralizing signal, and
surgically implanted these cells into adult tail stumps -- leading to
the regeneration of perfect tails.

"This study has provided us with essential practice on how to improve an organism's regenerative potential," said Lozito. "Perfecting the imperfect regenerated lizard tail provides us with a blueprint for improving healing
in wounds that don't naturally regenerate, such as severed human limbs
and spinal cords. In this way, we hope our lizard research will lead to
medical breakthroughs for treating hard-to-heal injuries." Additional co-authors include Ricardo Londono and Aaron X. Sun from the University
of Pittsburgh School of Medicine, and Megan L. Hudnall from USC.

The work was made possible by grant R01GM115444 from the National
Institute of General Medical Sciences, one of the National Institutes
of Health.

========================================================================== Story Source: Materials provided by
University_of_Southern_California. Original written by Cristy Lytal. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Thomas P. Lozito, Ricardo Londono, Aaron X. Sun, Megan L. Hudnall.

Introducing dorsoventral patterning in adult regenerating lizard
tails with gene-edited embryonic neural stem cells. Nature
Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-26321-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211014141958.htm

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