The axolotl is a type of salamander known for its striking ability to
fully regenerate limbs following amputation. Despite the promise of axolotl research for human regenerative
medicine, the genomic resources currently available for axolotls remain
This is due in part to the large size and highly
repetitive nature of the organism's genome - indeed, it is roughly 10
times the size of the human genome. Propelled by recent advances in
genomic sequencing and bioinformatics, researchers have found an
alternative for identifying and studying axolotl genes: transcriptomes.
‘The "transcriptome" catalogue provides resource about salamander that promises to shed light on molecular mechanisms that underlie limb regeneration and potential ways to repair and replace human tissues.’
A research team led by scientists at Brigham and Women's Hospital has
assembled a catalogue of every active gene in a variety of tissues in
The catalogue, known as a
"transcriptome," provides a important resource for the community of
researchers who study axolotls - a model organism that promises to
shed light not only on the molecular mechanisms that underlie limb
regeneration but also how on potential ways to repair and replace human
tissues that are damaged or lost as a result of injury, illness, or even
"Our hope is that this new resource will help make axolotls
accessible not only to researchers who already work on the organism, but
also to those in other fields who wish to explore it," said Jessica
Whited, a senior author of the study and an assistant professor in
the Department of Orthopedic Surgery at BWH. "Unfortunately, the axolotl
has been largely impenetrable for the majority of scientists."
accomplish this goal, Whited and her collaborators, led by Brian Haas,
Senior Computational Biologist at the Broad Institute, are making their
data available through an easily navigable web portal.
In the last few years, a handful of axolotl transcriptome studies
have been published. What distinguishes the latest study is its
near-completeness, in terms of represented genes, and its coverage of
diverse tissues involved in limb regeneration, including bone and
cartilage, skeletal muscle, heart, and blood vessels. The researchers
also included different portions of the blastema, a cluster of cells
that forms shortly after limb amputation and directs the formation of a
complete new limb.
In addition to developing this valuable resource, Whited and her
colleagues also mined it to uncover important axolotl genes and
investigate the genes' potential functions. One interesting gene is
kazald1, which is very highly enriched in blastema cells. Although it
has been identified in mammals and has even been found in certain types
of tumors, virtually nothing is known about kazald1's function.
Because of the axolotl's relatively long generation time - it takes nine months for a newly-fertilized embryo to develop, grow, and become
sexually mature - traditional methods for deleting genes to understand
their effects are labor-intensive and daunting at large scale.
Therefore, the study's first author, graduate student Donald Bryant,
developed an innovative approach to modify, or "edit" genes solely in
the axolotl limb. Although the efficiency of the method needs to be
improved, future work in this area could help accelerate efforts to
elucidate the functions of scores of axolotl genes and, in turn, help
reveal the molecular steps required for limb regeneration.