William Brad Barbazuk

Adam: my response continues... So while it is true that mammals can regenerate individual tissues such as peripheral nerve and undergo compensatory hypertrophy there is no doubt that mammals have nowhere near the epimorphic abilities that salamanders do. In addition mammals tend to fibrose at the sites of damage even when regeneration does take place. It was very striking, therefore, when we discovered that the spiny mouse could regenerate ear punches and skin wounds perfectly and without fibrosis (Seifert et al., 2012). The regeneration of the ear punch is truly an epimorphic phenomenon involving a blastema just like that seen in salamander limb regeneration and the skin regenerates in a scar-free manner. In doing this regeneration a wide range of tissues are replaced in a perfectly co-ordinated fashion – hairs, sebaceous glands, cartilage, dermis, skeletal muscle, adipose tissue and without the occurrence of fibrosis. It seemed as if all these sporadic reports of regeneration in mammals had come together in one animal making the spiny mouse a truly remarkable organism. We are currently examining regeneration in other organs of the spiny mouse and obtaining some very exciting results which we feel adds to the uniqueness of this mammal. On the other hand it could be that epimorphic regeneration has actually evolved many times in mammals and the spiny mouse is not at all unique, but scientists have not sampled the more than 5000 species of mammals widely enough to examine this proposition because of our mistaken(?) notion that mammals cannot regenerate so nobody bothers to do the experiments. Whichever the case may be, at the present time, there is no doubt that the spiny mouse can regenerate epimorphically without scarring and therefore represents a very exciting and valuable resource worthy of further study.

Dear Adam, you are, of course, correct in your comments as all animals on the planet can undergo some form of regeneration, known as physiological regeneration, to maintain homeostasis. The continual replacement of blood cells from the bone marrow, the continual replacement of epidermal cells from the basal layers of the skin, the continual replacement of the gut epithelial lining from the stem cells in the crypts are examples of this phenomenon. Cellular regeneration also occurs in all animals. But when you consider the occurrence of reparative regeneration or epimorphic regeneration of complex, multi-tissue organs most people would say that this does not occur in higher vertebrates such as mammals, but it is a phenomenon restricted to lower vertebrates and these are the organisms in which complex reparative regeneration is studied – fin, heart and brain regeneration in zebrafish, tail regeneration in lizards, and between newts and axolotls they can regenerate virtually every organ – heart, brain, spinal cord, lens, retina, tails, limbs, skin, lower jaw. While no mammal can match this unsurpassed ability of newts and salamanders there is some striking reparative regenerative ability that exists in the individual organs of mammals in addition to the physiological regeneration described above. As you point out these include peripheral nerve regeneration and scarless healing of the oral mucosa. The liver and the lung can respond to removal of a part of that organ by expansion of the remaining part in a process known as compensatory hypertrophy which is not regarded as epimorphic regeneration. But in addition to that there are sporadic reports of true epimorphic regeneration such as the regeneration of through-and-through ear punches in rabbits (first reported in the 1950s) and where on this spectrum of regeneration definitions do you put the annual regrowth of antlers in deer by a process involving a blastema and a rate of bone regrowth outstripping any other vertebrate?

Hi Tim, Classical genetics should be possible, but there are no well established lab lines not genotyping as of yet. Here are some links to some recent papers you may find interesting! http://www.nature.com/nature/journal/v489/n7417/full/nature11499.html http://onlinelibrary.wiley.com/doi/10.1111/wrr.12385/full http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142931

Hi Tim - thanks for you interest and your question. So, we are really interested in doing a complete genome + annotation - and we are seeking support from additional funding sources to do this. For this competition we are requesting the materials to do a deep PacBio IsoSeq transcriptome. Our rationale is that this is something that can be done well given the size of the sequencing support being awarded, and it is immediately useful to us and the community, while a partial genome sequence may be less useful. I do agree with you that deprh of the PacBio transcriptome may not be high enough to quantify low expressed genes, but we are actually more interested in it as a means to provide a reference. We have already acquired very deep illumina short-read sequence from RNA samples collected at multiple time points during healing (and in multiple replicates). We can (and have) run several assembly procedures on this. Unfortunately without a genome reference there is always concern that the assemblies are inaccurate and partial, and we have many 'transcripts' that fall into this. We are hoping that deep PacBio data will greatly improve our assemblies, as well as help identify transcript isoforms - many of which I am sure we are collapsing in our short read assemblies. If we can get a decent transcriptome reference then we should have a good catalogue of spiny's genes. In addition, this reference will allow us to make proper use of our deep short-read data, and we will be able to quantitatively inform on gene expression during the healing process. All of this (PacBio + Illumina sequence, assemblies, quantification and analysis will be placed into the public domain!