Biology Reference
In-Depth Information
liver will provide further insight into the molecular pathways that
drive the early growth response of the liver and “prime” quiescent
hepatocytes to reenter the cell cycle and proliferate.
Complement and Regenerative Pathways in Lower Vertebrates
The ability to regenerate complex structures and reconstruct entire
body parts from damaged tissues is a trait widely encountered among
invertebrates (e.g., annelids, hydroids, etc.) and in lower vertebrates
such as amphibians [80]. In urodele amphibians (axolotls) the process
of regeneration is quite prominent in the limb, tail, and in structures of
the eye (retinal epithelium and lens) [81,82]. Limb regeneration in
urodeles entails the activation of complex developmental pathways
that act in concert to promote dedifferentiation, proliferation, and
redifferentiation of mesenchymal cells into the specific cell types that
comprise the various tissues of the regenerating limb.
The molecular pathway(s) that underlie these developmental stages
are largely unknown. Surprisingly, a recent study implicated comple-
ment component C3 in urodele regeneration by showing specific
expression of C3 in the blastema cells located in the regenerative zone
of the amputated limb [83].
To determine the impact of complement in urodele regeneration and
to dissect the specific involvement of the critical components C3 and
C5 in limb and lens regeneration, studies were performed using the
newt (
Notophthalmus viridescens
) as a model organism that possesses
extensive regerative capacity in both these tissues. To monitor the
expression of complement proteins during newt lens and limb regener-
ation, newt cDNAs for complement C3 and C5 were isolated and used
for the generation of antibodies against C3a and C5a; these antibodies
were shown to be specific for C3 and C5, respectively, and found to
inhibit their activation [84]. Expression of both proteins was demon-
strated in limb and lens structures during regeneration by
immunostaining using the respective polyclonal antibodies. The
expression of C3 and C5 was also confirmed by in situ hybridization.
To assess the in vivo role of complement in regeneration, cobra
venom factor was injected into newts before amputation and found to
cause a significant delay in limb regeneration. In contrast, similar treat-
ment before lentectomy resulted in bigger fiber formation in the lens.
To dissect the role of C3 and C5 in regeneration, further studies are in
progress to analyze the effect of anti-C3a and C5a antibodies in both
limb and lens regeneration [85].
A Role for Complement in Hematopoietic Development
and Stem Cell Engraftment
The role of various complement regulatory molecules and receptors in
protecting blood cells from complement-mediated lysis and promoting
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