Forsyth Scientists Discover Early Key To Regeneration
Science may be one step closer to understanding how a limb can be
grown or a spinal cord can be repaired. Scientists at The Forsyth
Institute have discovered that some cells have to die for regeneration
to occur. This research may provide insight into mechanisms necessary
for therapeutic regeneration in humans, potentially addressing tissues
that are lost, damaged or non- functional as a result of genetic
syndromes, birth defects, cancer, degenerative diseases, accidents,
aging and organ failure. Through studies of the frog (Xenopus) tadpole,
the Forsyth team examined the cellular underpinnings of regeneration.
The Xenopus tadpole is an ideal model for studying regeneration because
it is able to re-grow a fully functioning tail and all of its
components, including muscle, vasculature, skin, and spinal cord. The
Forsyth scientists studied the role that apoptosis, a process of
programmed cell death in multi-cellular organisms, plays in
regeneration. The research team, led by Michael Levin, Ph.D., Director
of the Forsyth Center for Regenerative and Developmental Biology, found
that apoptosis has a novel role in development and a critical role in
regeneration. According to Dr. Levin, "Simply put, some cells have to
die for regeneration to happen."
The findings will be published in the January 1, 2007 issue of
Developmental Biology (v301i1). "We were surprised to see that some
cells need to be removed for regeneration to proceed," said Ai-Sun
Tseng, Ph.D. the paper's first author. "It is exciting to think that
someday this process could be managed to allow medically therapeutic
regeneration."
Summary of Study
In the context of efforts to understand biophysical controls of
regenerative processes, The Forsyth Center for Regenerative and
Developmental Biology investigated the dynamics of cell number control
in the regenerating tail bud. Previous research in the field has shown
that one mechanism by which cell number is controlled is by programmed
cell death, which has been shown to be involved in sculpting of growing
tissue in a number of developmental systems including heart, limb and
craniofacial patterning. This study shows that despite the massive
tissue proliferation required to build the tail, an early apoptotic
event is required for regeneration. Normal regeneration of the tail
includes a small focus of apoptotic cells; when apoptosis is inhibited
during the first 24 hours, regeneration cannot proceed and the growth
of nerve axons becomes abnormal. Later inhibition of apoptosis has no
effect, suggesting that the programmed death of a specific cellular
component is a very early step in the regeneration program. One
possible model is that tissues normally contain a population of cells
whose purpose is to prevent massive growth in the region surrounding
them. Future work by the Levin group will identify the cells that must
die, in order to try to understand the signals that cells utilize for
growth control.
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Michael Levin, PhD. is an Associate Member of the Staff in The Forsyth
Institute Department of Cytokine Biology and the Director of the
Forsyth Center for Regenerative and Developmental Biology. Through
experimental approaches and mathematical modeling, Dr. Levin and his
team examine the processes governing large-scale pattern formation and
biological information storage during animal embryogenesis. The lab's
investigations are directed toward understanding the mechanisms of
signaling between cells and tissues that allows a living system to
reliably generate and maintain a complex morphology. The Levin team
studies these processes in the context of embryonic development and
regeneration, with a particular focus on the biophysics of cell
behavior.
The Forsyth Institute is the world's leading independent organization
dedicated to scientific research and education in oral, craniofacial
and related biomedical sciences.
Contact: Jennifer Kelly
Forsyth Institute
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