including several reviews (García-Arrarás and Greenberg 2010; García-Arrarás
and Dolmatov 2010; Mashanov and García-Arrarás 2011). The initial description
of the process was published over a decade ago (García-Arrarás et al. 1998). Many
of the subsequent articles describe cellular events that take place during the process, including extracellular remodelling (Quiñones et al. 2002), cell migration
(Cabrera-Serrano and García-Arrarás 2004; García-Arrarás et al. 2006), myogenesis (Murray and García-Arrarás 2004), cell dedifferentiation (Candelaria et al.
2006), cell division (García-Arrarás et al. 1998), apoptosis (Mashanov et al. 2010a,
b) and epithelial to mesenchymal transitions (García-Arrarás et al. 2011). Many of
the cellular events are now well understood and have been integrated in a working
model (see Mashanov and García-Arrarás 2011, García-Arrarás et al. 2011). In
brief, following evisceration cells of the mesentery mesothelium, particularly
myocytes, dedifferentiate and migrate as a cell layer toward the free end of the
mesentery, where the intestine was previously attached, prior to evisceration.
As cells migrate, some undergo proliferation while others ingress into the connective tissue and provide cells for the formation of the intestinal rudiment. This
gives rise, initially, to a solid rod of tissue that extends from the oesophagus to the
cloaca. Luminal cells from the oesophagus and cloaca migrate into this tissue rod
forming the luminal layer and thus, the lumen of the intestine. Once the initial
rudiment is formed, cells from the mesothelium differentiate, giving rise to the
muscle cells (Murray and García-Arrarás 2004) and possibly to neurons. A comparison to other regenerative processes, such as wound healing of the body wall,
has shown that the same cellular events are common to both (San Miguel-Ruiz and
García-Arrarás 2007).
In recent years, experiments have aimed at understanding the molecular basis of
intestinal regeneration. Many of these experiments are summarized below. The
experimental data indicate a large number of genes are associated with intestinal
regeneration; over 70 % of the studied sequences showed some type of differential
expression between regenerating and normal intestines (Ortiz-Pineda et al. 2009).
Nervous System Regeneration
One of the main research interests of the García-Arrarás laboratory has been the
regeneration of the nervous system. The main reason is that this type of regeneration is highly limited in vertebrates and most other chordates. Nonetheless,
echinoderms with their amazing regenerative potential should provide excellent
models to study nervous system regeneration. Many of the investigations carried
out in the laboratory centered on this topic. Thus, neuronal markers were developed and the neuroanatomy of the holothurians was described. Even early
experiments on intestinal regeneration (García-Arrarás et al. 1998) were initiated
with an interest in the enteric nervous system, that is, the nervous system of the
digestive tract. Results have shown that H. glaberrima can regenerate its enteric
nervous system and that this regeneration occurs concomitantly with the regeneration of the intestine itself (García-Arrarás et al. 1999). Additional experiments
14 Review of Echinoderm Research in Puerto Rico
451
and Dolmatov 2010; Mashanov and García-Arrarás 2011). The initial description
of the process was published over a decade ago (García-Arrarás et al. 1998). Many
of the subsequent articles describe cellular events that take place during the process, including extracellular remodelling (Quiñones et al. 2002), cell migration
(Cabrera-Serrano and García-Arrarás 2004; García-Arrarás et al. 2006), myogenesis (Murray and García-Arrarás 2004), cell dedifferentiation (Candelaria et al.
2006), cell division (García-Arrarás et al. 1998), apoptosis (Mashanov et al. 2010a,
b) and epithelial to mesenchymal transitions (García-Arrarás et al. 2011). Many of
the cellular events are now well understood and have been integrated in a working
model (see Mashanov and García-Arrarás 2011, García-Arrarás et al. 2011). In
brief, following evisceration cells of the mesentery mesothelium, particularly
myocytes, dedifferentiate and migrate as a cell layer toward the free end of the
mesentery, where the intestine was previously attached, prior to evisceration.
As cells migrate, some undergo proliferation while others ingress into the connective tissue and provide cells for the formation of the intestinal rudiment. This
gives rise, initially, to a solid rod of tissue that extends from the oesophagus to the
cloaca. Luminal cells from the oesophagus and cloaca migrate into this tissue rod
forming the luminal layer and thus, the lumen of the intestine. Once the initial
rudiment is formed, cells from the mesothelium differentiate, giving rise to the
muscle cells (Murray and García-Arrarás 2004) and possibly to neurons. A comparison to other regenerative processes, such as wound healing of the body wall,
has shown that the same cellular events are common to both (San Miguel-Ruiz and
García-Arrarás 2007).
In recent years, experiments have aimed at understanding the molecular basis of
intestinal regeneration. Many of these experiments are summarized below. The
experimental data indicate a large number of genes are associated with intestinal
regeneration; over 70 % of the studied sequences showed some type of differential
expression between regenerating and normal intestines (Ortiz-Pineda et al. 2009).
Nervous System Regeneration
One of the main research interests of the García-Arrarás laboratory has been the
regeneration of the nervous system. The main reason is that this type of regeneration is highly limited in vertebrates and most other chordates. Nonetheless,
echinoderms with their amazing regenerative potential should provide excellent
models to study nervous system regeneration. Many of the investigations carried
out in the laboratory centered on this topic. Thus, neuronal markers were developed and the neuroanatomy of the holothurians was described. Even early
experiments on intestinal regeneration (García-Arrarás et al. 1998) were initiated
with an interest in the enteric nervous system, that is, the nervous system of the
digestive tract. Results have shown that H. glaberrima can regenerate its enteric
nervous system and that this regeneration occurs concomitantly with the regeneration of the intestine itself (García-Arrarás et al. 1999). Additional experiments
14 Review of Echinoderm Research in Puerto Rico
451