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
Our aim is to understand at the molecular and cellular level how an axolotl spinal cord can functionally repair after injury and why mammals cannot. To this end we have used transcriptional profiling to identify key differences at the miRNA level between axolotl and rat after spinal cord injury. In particular we are focusing on the differences between the rostral and caudal sides of the injury site and how the axolotl creates a permissive environment for axonal regrowth while mammals do not. We are focusing not just on the neuronal cells but also on the contribution and interaction of the other cells especially endothelial cells and skin to this repair process.
In addition to understanding spinal cord repair we are also interested in elucidating conserved pathways used for all regenerative processes like limbs, heart, pancreas etc as well as those which tell cells at a cut surface what and how much needs to be regenerated.
Erickson JR, Gearhart M, Honson D*, Moriarity BS and Echeverri K. A novel role for SALL4 during scar free wound healing in axolotl. NPJ Regenerative Medicine, 8th December 2016, doi:10.1038/npjregenmed.2016.16
Diaz Quiroz J, Li Y, Aparicio C and Echeverri K. Development of 3D matrix for modeling mammalian spinal cord injury in vitro. Neural Regeneration Research, November 2016,Volume 11,Issue 11. doi: 10.4103/1673-5374.194751
Sabin K, Santos-Ferreira T, Essig J, Rudasill S*, Echeverri K. Dynamic membrane depolarization is an early regulator of glial cell response to spinal cord injury. Dev. Biol. 2015 Dec 1;408(1):14-25. PMID:26477559.
Gearhart MD, Erickson JR, Walsh A, Echeverri K.(2015). Identification of Conserved and Novel MicroRNAs during Tail Regeneration in the Mexican Axolotl. Int J Mol Sci. 2015 Sep 11;16(9):22046-61. PMID:26378530
Diaz Quiroz JF, Tsai E, Coyle M, Sehm T, Echeverri K (2014) Precise control of miR-125b levels is required to create a regeneration-permissive environment after spinal cord injury: a cross-species comparison between salamander and rat. Dis Model Mech. 7(6):601-11.
Diaz Quiroz JF, Echeverri K. (2013) Spinal cord regeneration: where fish, frogs and salamanders lead the way, can we follow? Biochem J. 451(3):353-64. doi: 10.1042/BJ20121807.
Sehm T, Sachse, C , Frenzel, C and Echeverri K. miR-196 is an essential early-stage regulator of tail regeneration, upstream of key spinal cord patterning events. Dev Biol. 2009 Oct 15;334(2):468-80. Epub 2009 Aug 13
Echeverri, K and EM Tanaka. 2005. Proximodistal Patterning during Limb Regeneration. Dev. Biol. 279(2):391-401.
Echeverri, K. and EM Tanaka. 2002. Ectoderm to Mesoderm Lineage Switching during Axolotl Tail Regeneration.Science 298: 1993-1996
Echeverri K, Tanaka EM. Mechanisms of muscle dedifferentiation during regeneration.Semin Cell Dev Biol. 2002 Oct;13(5):353-60. Review.
Echeverri, K., Clarke, JD and EM Tanaka. 2001. In vivo imaging indicates muscle fiber dedifferentiation is a major contributor to the regenerating tail blastema.Dev. Biol. 236 (1):151-64.