Abstract
The Mexican Axolotl is able to regenerate missing limb structures in any position along the limb axis throughout its life and serves as an excellent model to understand the basic mechanisms of endogenous regeneration. How the new pattern of the regenerating axolotl limb is established has not been completely resolved. An accumulating body of evidence indicates that pattern formation occurs in a hierarchical fashion, which consists of two different types of positional communications. The first type (Type 1) of communication occurs between connective tissue cells, which retain memory of their original pattern information and use this memory to generate the pattern of the regenerate. The second type (Type 2) of communication occurs from connective tissue cells to other cell types in the regenerate, which don't retain positional memory themselves and arrange themselves according to these positional cues. Previous studies suggest that molecules within the extracellular matrix (ECM) participate in pattern formation in developing and regenerating limbs. However, it is unclear whether these molecules play a role in Type 1 or Type 2 positional communications. Utilizing the Accessory Limb Model, a regenerative assay, and transcriptomic analyses in regenerates that have been reprogrammed by treatment with Retinoic Acid, our data indicates that the ECM likely facilities Type-2 positional communications during limb regeneration.
Highlights
Human limb loss can result directly from trauma or secondary to diseases, such as cancer and diabetes, and is associated with many physical, psychological, and financial burdens on the patient [1,2,3]
According to the Patterning Hierarchy Model of regeneration, Type 1 positional communications occur between connective tissue derived cells in the blastema in order to generate the missing positional information to complete the pattern of the regenerate
If these grafts result in the formation of ectopic limb structures in both Accessory Limb Model (ALM) locations, this would indicate that new, stabile, positional information is generated by the extracellular matrix (ECM) grafts
Summary
Human limb loss can result directly from trauma or secondary to diseases, such as cancer and diabetes, and is associated with many physical, psychological, and financial burdens on the patient [1,2,3]. One of the major goals of regenerative medicine is to engineer a means to repair missing limb tissues endogenously within the human body. A variety of model organisms, which unlike humans exhibit robust regenerative ability, are utilized to assess the requirements and mechanisms of innate regeneration in the hopes of achieving this goal. Limb regeneration has been extensively studied in the Mexican axolotl (Ambystoma mexicanum), a urodele amphibian. This process involves the formation of a transient regenerative organ known as the blastema, constituted by dedifferentiated limb progenitor cells and the appropriate molecular signals.
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