The limb is a complex structure that consists of numerous tissue types such as epidermis, bones, muscles, fibroblasts, nerves, vasculature and immune cells. Upon limb amputation all these cell types coordinate with each other and carry out an extraordinary feat of restoring exactly the lost portion. How do the cells even know where the amputation was made? How do they know when to stop regenerating? How do they form an exact replica with all the proper skeletal elements? These are just some of the questions that keep us busy.
Axolotl is one of the few organisms that can regenerate their primary body axis including spinal cord. During embryonic development, an array of myotomes and vertebrae is formed through a segmentation process called somitogenesis. Upon tail amputation axolotls also recreate new segments, each containing new muscles and vertebrae. However, these segments originate from a mature tissue and in the absence of somites. Using state of the art technologies, we are addressing questions such as; what is the cellular source of the tail blastema and what are the underlying molecular mechanisms of tail regeneration.
Axolotls are full of wonders. Although they spend most of their life in neoteny, in the lab they are capable of metamorphosis. A single exposure to L-thyroxine transforms axolotl body – they retract their gills and start breathing with their lungs. During metamorphosis they shed their skin and the emerging skin is more compatible with the terrestrial habitat. They lose their fin and their tail rounds up. Interestingly, they can still display tissue regeneration ability, although there is a small decline in the rate and fidelity. We want to understand the cellular and molecular basis for metamorphosis and its implication on tissue regeneration.
How wonderful it would be, if we do not have to deal with the opacity of tissues and organs. Just a thought that we can see through regenerating tissue is breathtaking. While nature has made few transparent organisms, most models are non-transparent. However, by understanding the principles of light behaviors and its interaction with various substances/chemicals, we can achieve high level of transparency in fixed tissues. Our lab is constantly investigating these principles and leveraging it to perform whole mount imaging to perform snapshots of regeneration.