José E San Miguel-Ruiz, Angel R Maldonado-Soto and José E García-Arrarás
Department of Biology, University of Puerto Rico, Rio Piedras, Puerto Rico
BMC Developmental Biology 2009,
9:3. [Open Access]
Regeneration of neurons and fibers in the mammalian spinal cord has
not been plausible, even though extensive studies have been made to
understand the restrictive factors involved. New experimental models
and strategies are necessary to determine how new nerve cells are
generated and how fibers regrow and connect with their targets in adult
animals. Non-vertebrate deuterostomes might provide some answers to
these questions. Echinoderms, with their amazing regenerative
capacities could serve as model systems; however, very few studies have
been done to study the regeneration of their nervous system.
We have studied nerve cord regeneration in the echinoderm Holothuria glaberrima.
These are sea cucumbers or holothurians members of the class
Holothuroidea. One radial nerve cord, part of the echinoderm CNS, was
completely transected using a scalpel blade. Animals were allowed to
heal for up to four weeks (2, 6, 12, 20, and 28 days post-injury)
before sacrificed. Tissues were sectioned in a cryostat and changes in
the radial nerve cord were analyzed using classical dyes and
immmuohistochemistry. In addition, the temporal and spatial
distribution of cell proliferation and apoptosis was assayed using BrdU
incorporation and the TUNEL assay, respectively.
We found that H. glaberrima can regenerate its radial nerve
cord within a month following transection. The regenerated cord looks
amazingly similar in overall morphology and cellular composition to the
uninjured cord. The cellular events associated to radial cord
regeneration include: (1) outgrowth of nerve fibers from the injured
radial cord stumps, (2) intense cellular division in the cord stumps
and in the regenerating radial nerve cords, (3) high levels of
apoptosis in the RNC adjacent to the injury and within the regenerating
cord and (4) an increase in the number of spherule-containing cells.
These events are similar to those that occur in other body wall tissues
during wound healing and during regeneration of the intestine.
Our data indicate that holothurians are capable of rapid and
complete regeneration of the main component of their CNS. Regeneration
involves both the outgrowth of nerve fibers and the formation of
neurons. Moreover, the cellular events employed during regeneration are
similar to those involved in other regenerative processes, namely wound
healing and intestinal regeneration. Thus, holothurians should be
viewed as an alternative model where many of the questions regarding
nervous system regeneration in deuterostomes could be answered.