Temporal and Spatial Requirements of unplugged/MuSK Function during Zebrafish Neuromuscular Development

PLoS One

Laura R. Gordon¹  Michael Granato²  Lili Jing²  Elena Shtibin² 

[1] Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America;Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America

关键词: Embryos;    Synapses;    Axon guidance;    Muscle proteins;    Axons;    Muscle cells;    Zebrafish;    Developmental signaling;   

DOI  :  10.1371/journal.pone.0008843

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

One of the earliest events in neuromuscular junction (NMJ) development is the accumulation of acetylcholine receptor (AChR) at the center of muscle cells. The unplugged/MuSK (muscle specific tyrosine kinase) gene is essential to initiate AChR clustering but also to restrict approaching growth cones to the muscle center, thereby coordinating pre- and postsynaptic development. To determine how unplugged/MuSK signaling coordinates these two processes, we examined the temporal and spatial requirements of unplugged/MuSK in zebrafish embryos using heat-shock inducible transgenes. Here, we show that despite its expression in muscle cells from the time they differentiate, unplugged/MuSK activity is first required just prior to the appearance of AChR clusters to simultaneously induce AChR accumulation and to guide motor axons. Furthermore, we demonstrate that ectopic expression of unplugged/MuSK throughout the muscle membrane results in wildtype-like AChR prepattern and neuromuscular synapses in the central region of muscle cells. We propose that AChR prepatterning and axonal guidance are spatio-temporally coordinated through common unplugged/MuSK signals, and that additional factor(s) restrict unplugged/MuSK signaling to a central muscle zone critical for establishing mid-muscle synaptogenesis.

【 授权许可】

CC BY