Regeneration in zebrafish lateral line neuromasts: expression of the neural progenitor cell marker sox2 and proliferation-dependent and-independent mechanisms of hair cell renewal.
Mechanosensory hair cells are essential for audition in vertebrates, and in many species, have the capacity for regeneration when damaged. Regeneration is robust in the fish lateral line system as new hair cells can reappear after damage induced by waterborne aminoglycoside antibiotics, platinum-based drugs, and heavy metals. Here, we characterize the loss and reappearance of lateral line hair cells induced in zebrafish larvae treated with copper sulfate using diverse molecular markers. Transgenic fish that express green fluorescent protein in different cell types in the lateral line system have allowed us to follow the regeneration of hair cells after different damage protocols. We show that conditions that damage only differentiated hair cells lead to reappearance of new hair cells within 24 h from nondividing precursors, whereas harsher conditions are followed by a longer recovery period that is accompanied by extensive cell division. In order to characterize the cell population that gives rise to new hair cells, we describe the expression of a neural stem cell marker in neuromasts. The zebrafish sox2 gene is strongly expressed in neuromast progenitor cells, including those of the migrating lateral line primordium, the accessory cells that underlie the hair cells in neuromasts, and in interneuromastic cells that give rise to new neuromasts. Moreover, we find that most of the cells that proliferate within the neuromast during regeneration express this marker. Thus, our results describe the dynamics of hair cell regeneration in zebrafish and suggest the existence of at least two mechanisms for recovery of these cells in neuromasts.
Hernández
Pedro P
PP
Millennium Nucleus in Developmental Biology, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile.
Olivari
Francisco A
FA
Sarrazin
Andrés F
AF
Sandoval
Pablo C
PC
Allende
Miguel L
ML
D000818:Animals; D030801:Animals, Genetically Modified; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000633:toxicity; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D024002:HMGB Proteins / Q000096:biosynthesis* / Q000235:genetics; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053403:Lateral Line System / Q000502:physiology*; D008938:Mitosis / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D055748:SOXB1 Transcription Factors; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015027:Zebrafish
D000963:Antimetabolites; D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D003300:Copper; D001973:Bromodeoxyuridine