Experimental design of microRNA analysis of lizard tail regeneration. a: Image of a green anole lizard with a fully regenerated tail (arrow at break point). b: A 25 dpa regenerating tail was divided into three equally sized segments, with the distal regenerating tip and proximal regenerating base collected for microRNA sequencing (sequenced each for the regenerating tail tip and base, n = 3 per pool). For qRT-PCR analysis, five equally sized segments were collected (n = 4). c: Venn diagram showing the distribution of microRNAs expressed in the brain, skeletal muscle, and 25 dpa regenerating tail tip and base (minimum count of 1)
Findings from lizards may impact future therapies to regrow organs in humans. Any kid who pulls on a lizard tail knows it can drop off to avoid capture, but how they regrow a new tail remains a mystery. Now, researchers at the Translational Genomics Research Institute (TGen) and Arizona State University (ASU) have identified tiny RNA switches, ie microRNAs, which may hold the keys to regenerating muscles, cartilage and spinal columns.
3 microRNA’s, which turn genes on and off were found to be associated with the regeneration of tails in the green anole lizard, Anolis carolinensis. Using next-generation genomic and computer analysis, this interdisciplinary team of scientists hope their findings, following nearly 6 years of research, will help lead to discoveries of new therapeutic approaches to switch on regeneration genes in humans.
microRNAs and their co-expressed mRNA targets in the 25 dpa regenerating lizard tail. a–b: A treemap overview of significant (p < 0.05) Gene Ontology Biological Processes for downregulated microRNAs and their upregulated mRNA targets in the 25 dpa regenerating tail tip (a) and regenerating tail base (b). c–d: A treemap overview of significant (p < 0.05) Gene Ontology Biological Processes for upregulated microRNAs and their upregulated mRNA targets in the 25 dpa regenerating tail tip (c) and regenerating tail base (d). The relative sizes of the treemap boxes are based on the |log10(p-value)| of the respective GO term. Related terms are visualized with the same color, with the representative category for each color group denoted in the legend
“Since microRNAs are able to control a large number of genes at the same time, like an orchestra conductor leading the musicians, we hypothesized that they had to play a role in regeneration,” said Dr. Kenro Kusumi. “Our earlier work found that hundreds of genes are involved in regeneration, and we are very excited to study these three new microRNAs.”
Dr. Elizabeth Hutchins, a Post-Doctoral Fellow in TGen’s Neurogenomics Division, and co-lead author of the study, said she hopes this investigation eventually enables such things as regenerating cartilage in knees, repairing spinal cords in accident victims, and reproducing the muscles of injured war veterans.
“This work highlights the importance of tiny RNA molecules in the tissue regeneration process, and showed for the first time an asymmetric microRNA distribution in different portions of the regenerating lizard tails,” said Dr. Marco Mangone. “It seems like microRNAs may play an active role in this process, and are potentially able to shape the regenerating lizard tail like playdough.” https://www.tgen.org/home/news/2016-media-releases/lizard-tails-point-way-to-human-regeneration.aspx http://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-016-2640-3
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