Replacement of lateral line sensory organs during tail regeneration in salamanders: identification of progenitor cells and analysis of leukocyte activity

Abstract

It has been proposed that supporting cells may be the progenitors of regenerated hair cells that contribute to recovery of hearing in birds, but regeneration is difficult to visualize in the ear, because it occurs deep in the skull. Hair cells and supporting cells that are comparable to those in the ear are present in lateral line neuromasts, and in axolotl salamanders these cells are accessible to microscopic observation in vivo. After amputation of a segment of the tail that contains neuromasts, cells from the posteriormost neuromast on the tail stump divide rapidly and form a migratory regenerative placode. The cells of the regenerative placode represent a lineage that eventually produces both hair cells and supporting cells in replacement neuromasts. We sought to identify the progenitors of the regenerative placode by using differential interference contrast microscopy combined with time-lapse video recording in living axolotl salamanders. In response to amputation, the mantle-type supporting cells at the posteroventral edge of the neuromast that is nearest to the wound increased their frequency of cell division, and gave rise to the first cells of the placode. The increase in mitotic activity of mantle-type supporting cells was accompanied by an unexplained decrease in the frequency of divisions in the same neuromast's population of internal supporting cells. The time-lapse records suggested that the changes in the mitotic activity of supporting cells might have been linked to the presence of phagocytic leukocytes in the vicinity of the neuromast that was nearest to the wound. Leukocytes were evenly distributed around control neuromasts, but during regeneration leukocyte activity increased significantly in the vicinity of the posterior half of the posteriormost neuromast. The redistribution of leukocytes occurred early in the regenerative response, but a causal role for the leukocytes has not been conclusively established. It is possible that the leukocytes could contribute to the formation of the regenerative placode at that location by breaking down the glycocalyx that ensheaths the outermost cells of the neuromast, or through the secretion of mitogenic growth factors.

Hair Cell Differentiation in Chick Cochlear Epithelium after Aminoglycoside Toxicity:In VivoandIn VitroObservations

“…This hypothesis is supported by the fact that the timing and degree of cell division we detected in our cultures closely resemble those seen in vivo after a single injection of gentamicin or noise damage (Stone and Cotanche, 1994;Bhave et al, 1995). Although the proliferative capacity of support cells has not been determined, studies have shown that support cells are able to divide more than once after hair cell loss (Jones and Corwin, 1993;Stone and Cotanche, 1994;Presson, 1995).…”

Notch Signaling Regulates the Extent of Hair Cell Regeneration in the Zebrafish Lateral Line

“…In the nervous system, stem cells give rise to proliferating progenitors called transient amplifying cells, the progeny of which then differentiate (Alvarez-Buylla et al, 2001;Doetsch, 2003). In this study, we provide evidence for two distinct subpopulations of proliferating neuromast cells, designated as internal and peripheral SCs (Jones and Corwin, 1993;Williams and Holder, 2000). We suggest that internal SCs act as transient amplifying cells that give rise to new HCs during regeneration, whereas peripheral SCs may include a dedicated population of progenitor cells responsible for renewing the internal SC population.…”

“…With the aid of the SYTOX nuclear counterstain, BrdU-positive cells in three neuromasts (MI1, O1, and OP1) were subdivided as either internal or peripheral SCs based on their position within the neuromast (Fig. 2 D) (Jones and Corwin, 1993;Williams and Holder, 2000). Internal SCs are centrally located within the neuromast, whereas peripheral SCs lie along the periphery.…”

“…In the lateral line, regeneration occurs not only to renew lost HCs but also to renew whole neuromasts after they are removed, such as after tail amputation (Stone, 1937;Jones and Corwin, 1993;Dufourcq et al, 2006). In these instances, cells bud from the edge of existing neuromasts, proliferate, coalesce, and migrate to a new location to form new neuromasts in a manner recapitulating their development.…”

Manipulation of Neural Precursors in situ Induction of Neurogenesis in the Neocortex of Adult Mice

“…The medial cerebral cortex of lizards, which resembles the dentate gyrus of mammals, undergoes postnatal neurogenesis and can regenerate in response to injury (Lopez-Garcia et al 1992). Newts can regenerate their tails, limbs, jaws, and ocular tissues, and the neurons that occupy these regions (Jones and Corwin 1993;Brockes 1997). Goldfish undergo retinal neurogenesis throughout life (Johns and Easter 1977) and, impressively, can regenerate surgically excised portions of their retina in adulthood (Hitchcock et al 1992).…”