Galactosaminoglycans - Role in Brittlestar Limb Regeneration

• Main Author: Ramachandra, Rashmi
• Format: Doctoral Thesis
• Language: English
• Published: Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi 2012
• Subjects: Chondroitin sulfate; Dermatan sulfate; Brittlestar; Regeneration
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-179044; http://nbn-resolving.de/urn:isbn:978-91-554-8413-2

Regeneration is, in simple terms, ‘to re-grow’ damaged or lost parts of the body (e.g. cells, tissues and organs) and is a natural phenomenon occurring throughout the life of an organism. The regenerative capacity varies in the animal kingdom. Invertebrates have high regenerative capacity in contrast to higher vertebrates. This raises several fundamental questions related to the regeneration potential, evolutionary selection and its cellular and molecular mechanisms. An in-depth knowledge in regeneration is warranted to answer the fundamental questions that are still a challenge in regenerative medicine.  Glycosaminoglycans (GAGs) are known to be involved in various physiological processes. Of several GAG types galactosaminoglycans are the focus of this thesis. Galactosaminoglycans such as chondroitin sulfate/dermatan sulfate (CS/DS) are anionic linear polysaccharides covalently linked to core proteins so called proteoglycans (PGs), and form an integral part of both cell surface and extracellular matrix components. Although CS/DS have been associated with different cellular processes from development to homeostasis, not many studies have been carried out to understand their role in regeneration. In this thesis, we aim to study galactosaminoglycans, their structure, and interaction with growth factors of biological importance in the process of regeneration using simple invertebrate model organisms - brittlestars. We have identified CS/DS as the major GAG present in brittlestars. Molecular characterization of these chains indicated a much higher level of sulfation in Amphiura filiformis than so far found in GAGs from invertebrates or vertebrates. This brittlestar CS/DS promotes FGF2 mediated cell signaling similar to heparin. Further, we studied the functional role of these CS/DS chains and their biosynthetic machinery during arm regeneration in A. filiformis. Regeneration is followed by an increase in GAG sulfation from blastema stage to the fully functional arm. Suppressing sulfation on the other hand by sodium chlorate treatment drastically affected the proliferation process and thereby regeneration. Thus our findings suggest a potential biological role of CS/DS in brittlestar limb regeneration that may have relevance to regenerative medicine in future.