Dynamics of degeneration and regeneration in developing zebrafish peripheral axons reveals a requirement for extrinsic c
- PDF / 2,524,860 Bytes
- 15 Pages / 595.276 x 793.701 pts Page_size
- 33 Downloads / 161 Views
Villegas et al. Neural Development 2012, 7:19 http://www.neuraldevelopment.com/content/7/1/19
RESEARCH ARTICLE
Open Access
Dynamics of degeneration and regeneration in developing zebrafish peripheral axons reveals a requirement for extrinsic cell types Rosario Villegas1†, Seanna M Martin2†, Kelley C O’Donnell2, Simon A Carrillo1, Alvaro Sagasti2* and Miguel L Allende1*
Abstract Background: Understanding the cellular mechanisms regulating axon degeneration and regeneration is crucial for developing treatments for nerve injury and neurodegenerative disease. In neurons, axon degeneration is distinct from cell body death and often precedes or is associated with the onset of disease symptoms. In the peripheral nervous system of both vertebrates and invertebrates, after degeneration of detached fragments, axons can often regenerate to restore function. Many studies of axonal degeneration and regeneration have used in vitro approaches, but the influence of extrinsic cell types on these processes can only be fully addressed in live animals. Because of its simplicity and superficial location, the larval zebrafish posterior lateral line (pLL) nerve is an ideal model system for live studies of axon degeneration and regeneration. Results: We used laser axotomy and time-lapse imaging of pLL axons to characterize the roles of leukocytes, Schwann cells and target sensory hair cells in axon degeneration and regeneration in vivo. Immune cells were essential for efficient removal of axonal debris after axotomy. Schwann cells were required for proper fasciculation and pathfinding of regenerating axons to their target cells. Intact target hair cells were not themselves required for regeneration, but chemical ablation of neuromasts caused axons to transiently deviate from their normal paths. Conclusions: Macrophages, Schwann cells, and target sensory organs are required for distinct aspects of pLL axon degeneration or regeneration in the zebrafish larva. Our work introduces a powerful vertebrate model for analyzing axonal degeneration and regeneration in the living animal and elucidating the role of extrinsic cell types in these processes. Keywords: In vivo axotomy, Wallerian degeneration, Schwann cells, Leukocytes, Hair cells, Neurons, Lateral line
Background Axonal degeneration occurs during normal development of the nervous system and is central to the pathology of neurodegenerative diseases, nerve damage caused by metabolic diseases, and mechanical nerve injuries [1-3]. While there are different types of axonal degeneration, similar mechanisms regulate both developmental pruning of excessive axonal branches and the selective removal of damaged axons [1,4,5]. Wallerian degeneration (WD) * Correspondence: [email protected]; [email protected] † Equal contributors 2 Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA 1 FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Santiago, Chile
occurs in axon fragments that are
Data Loading...
