J Endocrinol Reprod 12 (2008) 2: 67 - 72 SUMMARY Epimorphic regeneration, as exemplified by lizard tail, involves the formation of regeneration blastema as a pre- requisite for replacement growth. The formation of blastema is preceded by many regressive changes like tissue demolition, histolysis, inflammation, wound closure, dedifferentiation, cell migration and proliferation. The ECM components of a normal tail help maintain the differentiated state of the constituent heterogeneous tissue and tend to prevent cell migration and proliferation. Since the formation of a regeneration blastema involves many key cellular events like dedifferentiation, migration of dedifferentiated and other nomadic cells and cell proliferation, extensive reorganization of the extracellular matrix is likely to be a major event during post-autotomy period. To this end, total GAG content and gelatinase (MMP-2 & 9) activity were assayed during the first week post-caudal autotomy. The effect of MMP inhibition by doxycycline was also evaluated in terms of the number of days taken for wound closure and blastema formation as well as the length of detail regenerated at the end of twenty days from the time of initiation of growth. Significant progressive decrement in total GAG content up till 96 hours followed by a significant increment at 120 and 144 hours, together with a biphasic increment in gelatinase activity (first during 24-48 hours and second during 96-144 hours) have been recorded. The increased gelatinase activity and the decreased GAG content in the first 96 hours are suggestive of breakdown of proteoglycans and collagens (type IV, V, VII & X). The second phase of increase in GAG content is related with synthesis of hyaluronate, favoring dedifferentiation, proliferation and migration of cells. MMP inhibition by doxycycline significantly retarded tail regeneration. From these results it is concluded that ECM remodeling is crucial in the immediate post-autotomy period for the formation of an effective blastema and that MMPs play a crucial role in the same. Key words: ECM remodeling, GAGs, lizard, MMPs, regeneration Assessment of extracellular matrix remodeling during tail regeneration in the lizard Hemidactylus flaviviridis V.V. Nambiar, I.Y. Bhatt, P.A. Deshmukh, R.R. Jape, P.N. Jivani, H.R. Kavale, S.S. Prakashkar and A.V. Ramachandran Division of Developmental and Reproductive Endocrinology, Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara - 390 002, India Correspondence to be addressed to: Dr. A.V. Ramachandran, Ph.D., Email: *avrcn@rediffmail.com Introduction Regeneration can be defined as the ability to reproduce relatively complicated organs or structures after they have been lost through trauma or other causes. Regeneration in lower invertebrates is essentially a mode of asexual reproduction while in higher invertebrates and vertebrates it is an adaptive mechanism essentially for replacement of lost part with functional exigency. Regenerative medicine has a challenging task of unraveling the secrets of how body parts can regenerate. The ability to shed or readily lose appendages as a method of escape from enemies, as in the case of lizard tail, is known as autotomy (self-amputation). The regeneration seen in higher vertebrates is epimorphic and the tropical lizard Hemidactylus flavivirdis is an excellent example showing epimorphic regeneration of its tail. Epimorphic regeneration is characterized by post-autotomy regressive (wound healing and dedifferentiation) and progressive (blastema and differentiation) phases. It is characterized by non- scarring type of wound healing and the formation of a regeneration blastema (akin to the embryonic tail bud) and redifferentiation and growth of tail (Ramachandran, 1996). Though the formation of a blastema is essential for replacement growth to occur, the immediate post- autotomy period is crucial for its establishment. Thus, the present study addresses an aspect of molecular intricacy in the immediate post-autotomy phase, which could aid in setting up an appropriate environment for the initiation of regeneration. A number of synchronized inter-related molecular events involving cytokines, growth factors, hormones and modifications of extracellular matrix (ECM) are likely to trigger the adaptive changes crucial for the early regressive phase of regeneration. It is known that there is loss of tissue organization at the cut end of the