Meeting Abstract
S5.9 Tuesday, Jan. 5 Bioelectric Events and Vertebrate Appendage Regeneration TSENG, A*; LEVIN, M; Tufts University; Tufts University aisun.tseng@tufts.edu
It has long been known that bioelectrical events play a causal role in vertebrate appendage regeneration. However, the underlying mechanisms have only recently begun to be revealed using the anuran frog, Xenopus laevis. Xenopus is able to regenerate its tail during development. The tail is a complex organ containing multiple cell types including muscle, nerve, spinal cord, and vasculature. After tail amputation, wound healing occurs by epithelial cell migration and is normally completed by 6 hours post amputation (hpa). By 24 hpa, a swelling called the regeneration bud is observed at the injury site and contains progenitors cells. Notably, amputated tails will regenerate fully with 7 days. A critical early event required for the initiation of tail regeneration is the activity of the proton pump, V-ATPase, which is expressed by 6 hpa (Adams et. al, 2007). A second ion transporter, a voltage-gated sodium channel (Nav1.2), is also required for the initiation of regeneration. Nav1.2 expression is dependent upon V-ATPase activity. In turn, Nav1.2 regulates the expression of genes (including Notch and Msx1) that drive regenerative outgrowth and patterning. Moreover, the regenerative process appears to directly respond to changes in the physiological state of the regeneration bud (i.e. changes in intracellular ion concentrations), and can bypass the requirement for ion channel activity. In fact, the pharmacological induction of a brief, transient sodium current into the regeneration bud after tail amputation is sufficient to restore full regeneration of the tail during the refractory period (an endogenous developmental period when regeneration is blocked). Thus modulation of ion transport is a key mechanism for controlling regeneration, and suggests that regulation of ion flows could represent an exciting new approach to tissue repair in mammals.
