Salamanders are capable of regenerating spinal cord tissue following transections, crushes, or amputations. Click here to see a time-lapse movie of axolotl tail regeneration over 45 days.
The figure below shows the external morphology of tail regeneration as well as the internal changes that are characteristic to appendage regeneration. The tissue sections on the right are coronal (viewed from the back of the animal downward) to show the sequence of events that will lead to complete regeneration. Notice the spinal cord in the middle of each section. Also notice that the wound epidermis has migrated over the exposed stump by 12 hours post amputation to close off the injury from the external environment. Cells near the injury site then start to proliferate to generate a structure called a blastema. Over the next several weeks, the blastema grows in a similar manner as limb regeneration except a new spinal cord is present in the middle of the tail blastema (hollow portion in 21 day histological section).
Over time, a spinal cord is completely regenerated including new nerve cells and the supporting cells necessary for proper motor control and sensory input. The image below shows the cells responsible for this process within a tail blastema. The red cells are neural progenitor cells that will eventually differentiate into new neurons, while the green labels inflammatory cells and the blue labels nuclei. Our research identifies, characterizes, and tests the function of genes that are expressed during spinal cord regeneration in order to understand the process at the cellular and molecular level. The hypothesis is that the cell types and gene expression patterns specific to the salamander compared to non-regenerating animals endow them with regenerative abilities.
STUDIES PERFORMED ON SPINAL CORD REGENERATION
Expression pattern of Nogo-A, MAG, and NgR in regenerating urodele spinal cord
Hiu SP, Monaghan JR, Voss SR, Ghosh S.
Dev Dynamincs. 2013 242(7):847-860.
Background: The mammalian central nervous system is incapable of substantial axon regeneration after injury partially due to the presence of myelin-associated inhibitory molecules including Nogo-A and myelin associated glycoprotein (MAG). In contrast, axolotl salamanders are capable of considerable axon regrowth during spinal cord regeneration. Results: Here, we show that Nogo-A and MAG, and their receptor, Nogo receptor (NgR), are present in the axolotl genome and are broadly expressed in the central nervous system (CNS) during development, adulthood, and importantly, during regeneration. Furthermore, we show that Nogo-A and NgR are co-expressed in Sox2 positive neural progenitor cells. Conclusions: These expression patterns suggest myelin-associated proteins are permissive for neural development and regeneration in axolotls.
Early gene expression during natural spinal cord regeneration in the salamander Ambystoma mexicanum.
Monaghan JR, Walker JA, Beachy CK, and Voss SR.
J Neurochem. 2007 101(1):27-40.
In contrast to mammals, salamanders have a remarkable ability to regenerate their spinal cord and recover full movement and function after tail amputation. To identify genes that may be associated with this greater regenerative ability, we designed an oligonucleotide microarray and profiled early gene expression during natural spinal cord regeneration in Ambystoma mexicanum. We sampled tissue at five early time points after tail amputation and identified genes that registered significant changes in mRNA abundance during the first 7 days of regeneration. A list of 1036 statistically significant genes was identified. Additional statistical and fold change criteria were applied to identify a smaller list of 360 genes that were used to describe predominant expression patterns and gene functions. Our results show that a diverse injury response is activated in concert with extracellular matrix remodeling mechanisms during the early acute phase of natural spinal cord regeneration. We also report gene expression similarities and differences between our study and studies that have profiled gene expression after spinal cord injury in rat. Our study illustrates the utility of a salamander model for identifying genes and gene functions that may enhance regenerative ability in mammals.