Elly Tanaka (IMP and VBC) 1: Axolotl Limb Regeneration

Summary

This research explores the fascinating process of limb regeneration in axolotls, particularly focusing on the role of different cell types. Key insights include the concept of 'positional memory' in bone-forming cells, which guide the regeneration process. Other cells, like Schwann and muscle cells, do not possess positional memory and rely on instructions from bone-forming cells. The study also highlights various experimental approaches, including genetic manipulation and cell tracing, to understand how cells regenerate and pattern limbs after amputation. This work has significant implications for regenerative medicine and tissue engineering.

Takeaways

• 😀 Salamanders have exceptional regenerative abilities, being able to regrow limbs, heart tissue, and other organs.
• 😀 Animals like hydra and worms can regenerate whole body parts, whereas more complex animals, such as lizards, regenerate only parts of limbs or tails.
• 😀 Axolotls (*Ambystoma mexicanum*) are a primary species used to study limb regeneration due to their clear skin mutants and impressive regeneration capabilities.
• 😀 The regeneration process involves the formation of a blastema, a mass of undifferentiated cells that grows and regenerates the missing limb parts.
• 😀 Regeneration in salamanders requires contributions from various tissues such as skin, muscle, nerve, and bone, each contributing to specific structures.
• 😀 Schwann cells, which are found in nerve tissue, play a vital role in the regenerative process, potentially dedifferentiating to contribute to tissue regrowth.
• 😀 Using transgenic axolotls with green fluorescent protein (GFP) enables researchers to trace cells during the regenerative process for detailed observations.
• 😀 Salamander cells have 'positional memory,' which means they know their original location in the limb, aiding in the proper regeneration of limb parts after amputation.
• 😀 Retinoic acid, a vitamin A derivative, can modify positional memory in cells, causing them to regenerate additional limb parts depending on its dosage.
• 😀 Key regulatory factors like MEIS and Prod1 are involved in determining the positional identity of cells during limb regeneration, ensuring correct tissue formation.
• 😀 Bone-forming cells retain their positional memory, contributing only to specific parts of the limb, while Schwann cells can help regenerate any part of the limb.

Q & A

What is the focus of Elly Tanaka's research on salamander limb regeneration?

Elly Tanaka's research focuses on understanding the process of limb regeneration in salamanders, particularly how cells from the adult limb are recruited to form the blastema and how the regenerated limb knows to form only the missing parts.

Which animals can regenerate parts of their bodies, and how does salamander regeneration differ?

Simple animals like hydra, worms, and flatworms can regenerate entire bodies after being cut in half. Lizards can regenerate their tails, and fish can regenerate fins, eyes, brain, and heart. Frogs can regenerate their tails and developing limbs. Salamanders, however, can regenerate not only limbs but also the jaw, tail, heart, brain, and internal organs, including the pancreas and kidney.

What makes the Mexican axolotl useful for studying limb regeneration?

The Mexican axolotl, or Ambystoma mexicanum, is useful for studying limb regeneration because it has remarkable regenerative abilities, is easy to breed, and allows researchers to observe the process of regeneration at a high resolution, especially when using transgenic animals expressing green fluorescent protein (GFP).

What are the main cell types involved in the regeneration of the salamander limb?

The main cell types involved in limb regeneration are epidermis cells, muscle cells, Schwann cells, nerve cells, bone-forming cells, and fibroblasts. These cells contribute to the formation of the blastema and play a role in regenerating the missing parts of the limb.

How does the blastema form during limb regeneration?

After a salamander limb is amputated, the remaining tissue forms a structure called the blastema, which is a mass of undifferentiated cells. These cells come from various tissues like muscle, bone, and skin and will proliferate and differentiate to regenerate the lost part of the limb.

What experiment demonstrated that Schwann cells could regenerate multiple cell types?

The experiment by Hugh Wallace and Malcolm Maden showed that Schwann cells, when transplanted into irradiated animals, could dedifferentiate and contribute to regenerating multiple cell types, not just Schwann cells, in the limb.

What role does green fluorescent protein (GFP) play in the research?

GFP is used in the research to trace and track the movements of specific cell types during regeneration. By using GFP-transgenic animals, researchers can observe which cells contribute to the regeneration process and study their behavior under the microscope.

What was the conclusion from experiments on muscle tissue during regeneration?

Experiments on muscle tissue revealed that muscle cells in the regenerating limb contribute only to muscle tissue. This shows that different tissues maintain their identity during regeneration, with muscle cells forming muscle and not other tissues like bone or skin.

How does the positional memory of cells affect limb regeneration?

Positional memory refers to a cell's ability to know its original location in the limb, and this memory guides the regeneration process. For example, bone-forming cells remember their position and regenerate the specific part of the limb from which they originated, while Schwann cells do not have positional memory and can contribute to all parts of the limb.

What is the role of retinoic acid in limb regeneration?

Retinoic acid, a derivative of vitamin A, plays a crucial role in overriding positional memory during regeneration. When injected into an amputated limb, it can cause cells to regenerate extra parts, such as the formation of an entire lower arm from a wrist amputation, by influencing the positional identity of cells.