Regeneration of sensory cells after laser ablation in the lateral line system: hair cell lineage and macrophage behavior revealed by time- lapse video microscopy

Abstract

The regeneration of sensory hair cells in lateral line neuromasts of axolotls was investigated via nearly continuous time-lapse microscopic observation after all preexisting hair cells were killed by a laser microbeam. The laser treatments left neuromasts with one resident cell type, which was supporting cells. Over the course of 1 week, replacement hair cells arose either directly via differentiation of cells present in the epithelium from the beginning of the time-lapse period or via the development of cells produced after one or two divisions of supporting cells. All of the cell divisions that produced hair cells were asymmetrical. During the first hour after the treatment, macrophages and smaller leukocytes were attracted to the laser-treated neuromasts. The smaller leukocytes returned to control levels 48-60 hr after the treatment, whereas macrophages remained active there throughout the period of hair cell replacement. Macrophage incidence peaked 36-48 hr after the laser treatment. Macrophages phagocytosed damaged hair cells and supporting cells, as well as new cells and preexisting cells without recognizable damage. The results provide direct evidence of hair cells arising as progeny produced from the divisions of supporting cells, evidence of hair cells and supporting cells arising from the same cell division, evidence relating to the timing of hair cell differentiation, and indirect evidence pertaining to proposals that hair cells sometimes arise via conversion of cells without an intervening division. The results also suggest that macrophages may influence early stages in the process of hair cell regeneration.

Auditory hair cell precursors immortalized from the mammalian inner ear

“…1993; Warchol et al 1993;Kelley et al 1995;Fekete 1996;Jones & Corwin 1996). During the ¢nal mitotic divisions, which occur in the mouse at E12^E14, pluripotent progenitors give rise to non-sensory precursors (NSP) and prosensory precursors (PSP).…”

Hair cell regeneration: An exciting phenomenon . . . But will restoring hearing and balance be possible?

“…The supporting cells then migrate through the sensory epithelium and regenerate by cell division (i.e., mitosis) [7,. During mitosis, one or more daughter hair cells are generated either through symmetrical differentiation, which produces two hair cells or two supporting cells [18,24,41], or asymmetrical differentiation that produces one hair cell and one supporting cell (Figure 2(a)) [27,31,38,41]. Alternatively, hair cells might convert or transdifferentiate from neighboring supporting cells through nonmitotic mechanisms (Figure 2(b)) [33,[51][52][53][54][55].…”

“…Resident macrophages recognize and destroy dying cells by engulfing them [58] and many secrete substances that may influence cell function [59]. Although the functional role of macrophages in the inner ear is unknown, numerous studies have demonstrated that macrophages and leukocytes reside in the undamaged sensory epithelia of the inner ear and are recruited to traumatized areas prior to the initiation of supporting cell proliferation [31,45,56,[60][61][62][63][64][65].…”

The lateral line of zebrafish: a model system for the analysis of morphogenesis and neural development in vertebrates

“…New hair cells can be generated during adult life in fish, amphibians and birds (but unfortunately not in the mammalian cochlea). Support cells can divide and form new hair cells (Jones and Corwin, 1996;Fekete et al, 1998;Lang and Fekete, 2001). The pattern of division and differentiation is not fixed, however, and a support cell can produce two support cells or one hair cell and one support cell.…”