Previous and current research

Throughout human life, many cells such as hair follicles and certain tissues such as liver can be continuously replaced to maintain tissue integrity in response to normal, daily wear and tear. However, the human response to more serious tissue damage, such as acute damage to limbs or to the spinal cord, is limited to relatively simple wound healing, whereby collagenous scar tissue fills the injury site, assuring the tissue’s structural integrity but often resulting in a debilitating loss of functional activity. While humans do exhibit some very limited regenerative capacity (e.g. finger tips), other vertebrates exhibit sometimes astonishing regenerative ability.

Salamanders show the highest diversity in being able to regenerate limbs, tail, heart, eyes and jaw, while other vertebrates like the zebrafish regenerate simpler structures like the heart and fins. In all cases, however, a central principle of all these processes is the generation of a population of pluripotent blastema cells, at least partly through dedifferentiation and migration of cells from neighbouring tissues, that will eventually differentiate and faithfully replace the lost structures. Indeed, if any upper limb of a urodele is amputated, for example, the animal faithfully regenerates an exact replica of the lost structure. How regeneration is “calibrated” so precisely remains unclear, though it is thought that cells at the cut surface maintain a positional memory of their identity and this stored information is then used to regenerate the missing structures, but the exact molecular basis underlying this process remains poorly understood.

We have recently carried out screens to identify genes that are involved in initiating the regenerative response in the salamander tail and limb. Functional analysis of these pathways are currently underway and are identifying genes that are specifically involved in the positional memory of cells at the amputation plane. We are also focusing on recently identified key post-translational regulators of major programs of gene expression, microRNAs. miRNAs are emerging as “micro-managers” of cells differentiation state in several organisms. We have identified key miRNAs in salamanders that are differentially regulated during regeneration and through in vivo manipulations are studying the exact roles for these miRNAs in limb and tail regeneration.

Future prospects and goals

• Molecular elucidation of the mechanisms underlying positional identity.

• Understanding the role of miRNAs in controlling genes necessary for initiation of regeneration.

• Characterisation of the role of specific miRNAs in positional memory.

Group Members

List of group members

Selected Publications

Echeverri, K and Oates AC. 2007. Coordination of symmetric cyclic gene expression during somitogenesis by Suppressor of Hairless involves regulation of retinoic acid catabolism. Dev Biol. 2007 Jan 15;301(2):388-403.

Echeverri, K and Tanaka, EM . 2005. Proximodistal Patterning during Limb Regeneration. Dev. Biol. 279(2):391-401.

Echeverri, K. and  Tanaka, EM. 2003. Electroporation as a Tool to Study In Vivo Spinal Cord Regeneration. Dev. Dyn. 226:418-425

Echeverri, K. and  Tanaka, EM. 2002. Ectoderm to Mesoderm Lineage Switching during Axolotl Tail Regeneration. Science 298: 1993-1996

Echeverri, K., Clarke, JD and  Tanaka, EM. 2001. In vivo imaging indicates muscle fiber dedifferentiation is a major contributor to the regenerating tail blastema. Dev. Biol. 236 (1):151-64.