The voltage-gated sodium channel (Na), Na1.1, is well-studied in the central nervous system; conversely, its contribution to peripheral sensory neuron function is more enigmatic. Here, we identify a new role for Na1.
View Article and Find Full Text PDFRegulation of cell cycle progression is essential for cell proliferation during regeneration following injury. After appendage amputation, the axolotl (Ambystoma mexicanum) regenerates missing structures through an accumulation of proliferating cells known as the blastema. To study cell division during blastema growth, we generated a transgenic line of axolotls that ubiquitously expresses a bicistronic version of the fluorescent ubiquitination-based cell-cycle indicator (FUCCI).
View Article and Find Full Text PDFThe size and shape of the tetrapod limb play central roles in their functionality and the overall physiology of the organism. In this minireview we will discuss observations on mutant animal models and humans, which show that the growth and final size of the limb is most impacted by factors that regulate either limb bud patterning or the elongation of the long bones. We will also apply the lessons that have been learned from embryos to how growth could be regulated in regenerating limb structures and outline the challenges that are unique to regenerating animals.
View Article and Find Full Text PDFThe mechanisms that regulate growth and size of the regenerating limb in tetrapods such as the Mexican axolotl are unknown. Upon the completion of the developmental stages of regeneration, when the regenerative organ known as the blastema completes patterning and differentiation, the limb regenerate is proportionally small in size. It then undergoes a phase of regeneration that we have called the 'tiny-limb' stage, which is defined by rapid growth until the regenerate reaches the proportionally appropriate size.
View Article and Find Full Text PDFLoss of regenerative capacity is a normal part of aging. However, some organisms, such as the Mexican axolotl, retain striking regenerative capacity throughout their lives. Moreover, the development of age-related diseases is rare in this organism.
View Article and Find Full Text PDFSome organisms, such as the Mexican axolotl, have the capacity to regenerate complicated biological structures throughout their lives. Which molecular pathways are sufficient to induce a complete endogenous regenerative response in injured tissue is an important question that remains unanswered. Using a gain-of-function regeneration assay, known as the Accessory Limb Model (ALM), we and others have begun to identify the molecular underpinnings of the three essential requirements for limb regeneration; wounding, neurotrophic signaling, and the induction of pattern from cells that retain positional memory.
View Article and Find Full Text PDFUrodele amphibians such as the axolotl regenerate complete limbs as adults, and understanding how the "blueprint", or pattern, of the regenerate is established and manipulated are areas of intense interest. Nutrient signaling plays an important role in pattern formation during regeneration. Retinoic acid signaling is the most characterized pathway during this process.
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