Anoles (Lizards) Key To Medically Applicable Regeneration?

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Anoles (Lizards) Key To Medically Applicable Regeneration?

http://www.medicalnewstoday.com/articles/211526.php

Anolis lizards first entered Arizona State University biologist Kenro Kusumi's

life in 1980 when, as a member of a junior curator program, he recorded in his

field notebook that he had found an Anolis egg on a field trip. Kusumi still has

those notes, along with other memorabilia that document the influence that both

his early life and more recent experiences have had on his current pursuits in

developmental biology. One such souvenir is a small Pueblo lizard sculpture that

sits on a table in his office. With one missing leg and a tail, broken and

repaired in two places, it is not particularly eye-catching, but it does

symbolize Kusumi's current research model: a lizard which can " fix " or more

accurately, regenerate, its broken tail.

Human regeneration is mainly limited to small portions of liver tissue, bone, or

muscle, yet understanding how regeneration occurs in other taxonomic groups may

enable scientists to improve human regenerative abilities in the future. Kusumi

is working to understand the molecular processes that enable some lizards to

regenerate their tissues with fellow ASU School of Life Sciences faculty members

Jeanne -Rawls, Allan Rawls, Fisher and Dale DeNardo (collectively

referred to as " JARKD " by their students).

Lizards can regenerate facial bones, certain areas of the spinal cord, and, as

is most commonly known, most lizards can regenerate their tail - including

muscles, cartilage, and spinal cord. The regenerated tail does not contain bone,

but instead is supported by a tube of hyaline cartilage - the same cartilage

humans have lining many of their joints. With widespread medical problems such

as arthritis and spinal cord injuries, the application of these regenerative

abilities is of extreme interest to medical institutions.

" Members of my family have terrible osteoarthritis, " Kusumi explains. " That

means the cartilage at the joints has degenerated. These lizards can regenerate

that kind of cartilage, and they have no problem doing so. How is it that we

can't do this, but they can? " With the help of the Anolis model, Kusumi and the

rest of the JARKD team are delving into this mystery, recently funded by a

$412,606 grant from the National Institutes of Health and a $225,000 grant from

the Arizona Biomedical Research Commission.

Many vertebrate and invertebrate species can regenerate tissues, but there are

several kinds of regeneration. Lizards most likely use stem-cell mediated

regeneration, where new cells involved in regrowth arise from tissue-specific

progenitor cells. This type of regeneration is the best bet for a regenerative

process compatible with the human system, Kusumi says. Now that the Anolis

carolinensis genome is sequenced, rather than trying to solve the puzzle blind,

the research team has a view of the bigger picture as a guide to work from.

Molecular methods have improved to the point that the JARKD team is focusing on

this question at the perfect time. Kusumi mused, " the beauty is that now we know

enough about development that we can actually have candidates for what cells are

making this new tail - we can have guesses as to what might be right. " Using

this candidate approach, -Rawls and graduate student Rajani have

successfully identified and isolated lizard cells that can make new muscle.

Meanwhile, the Kusumi lab is working to uncover what developmental control genes

are being expressed in regenerating tails. Here, with collaborators from the

Translational Genomics Research Institute (TGen), JARKD is using RNA-Seq, a

next-generation technology that allows researchers to take a more unbiased

approach, finding all the genes being expressed in a tissue at one point in

time. When compared with embryonic development of the tail, which is being

investigated by graduate student Walter Eckalbar, differences between initial

tissue generation and regenerative processes can be identified. The genes

involved in regeneration are likely conserved across various taxonomic classes,

but the genetic switches for those genes may be turned off or down. " Once we

understand the nuts and bolts of how this is happening, we can use available

technologies to manipulate and change that, " Kusumi explains, " then we will try

to translate that to the mouse model. "

A regenerating mouse tail is only one of the many images inspired by Kusumi's

Anolis studies. In concert with colleagues at the sonian Tropical Research

Institute (STRI) in Panama and Hutchins, one of Kusumi's graduate

students, the JARKD team is adopting an evolutionary perspective of various

Anolis processes or adaptations. " Occasionally you have a very unique

opportunity to look at a natural experiment where one species arrived on one

island or was isolated in a region, which then led to the adaptive radiation of

many species to fill a variety of niches, " Kusumi says. Anolis has in fact been

described by some scientists as the " Darwin's finch " of reptiles. This reference

points to the number and range of ecomorphs in the Anolis genus, as species have

arisen in different regions bearing highly similar behaviors and morphology

(also known as convergent evolution). While anoles have been the focus of many

evolutionary studies, the JARKD-STRI team is focusing on the intersection of

evolution and development, where " you can look for the regulatory changes that

drove a limb to be longer or muscles to be more robust. "

With such a bright road ahead for both the regenerative and evolutionary

undertakings, Kusumi hopes ASU will lead internationally, as a center for the

Anolis work. The opportunity to create such an interdisciplinary research

program attracted him in part to School of Life Sciences in ASU's College of

Liberal Arts and Sciences, which Kusumi describes as a place that " breaks down

the walls between disciplines. Of course, the realization of this vision depends

on complex collaborations, which Kusumi jokes are growing so large that listing

those not involved may be easier. Kusumi's Anolis collaborations go well beyond

JARKD, STRI, TGen and ASU, and also include some of Kusumi's undergraduate

mentees. Glenn Markov, a Barrett's Honors College undergraduate and member of

the School of Life Sciences Undergraduate Research (SOLUR) program, has spent

two years contributing to the ground work of the regeneration project. Much like

the tissue-specific process of human progenitor cells, each member of the

collaborative team - whether undergraduate, graduate student, or faculty - makes

unique contributions to ensure the creation of a functional end product.

Mark Twain once stated " a man who carries a cat by the tail learns something he

can learn in no other way. " In a similar vein, Kusumi, with lizard tail in hand,

may hold the most likely key to unlock the secrets of medically applicable

regeneration.

Source:

Margaret Coulombe

Arizona State University