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Retrograde regulation of motoneuron differentiation by muscle β-catenin

Nature Neuroscience volume 11, pages 262–268 (2008)Cite this article

Abstract

Synapse formation requires proper interaction between pre- and postsynaptic cells. In anterograde signaling, neurons release factors to guide postsynaptic differentiation. However, less is known about how postsynaptic targets retrogradely regulate presynaptic differentiation or function. We found that muscle-specific conditional knockout of β-catenin (Ctnnb1, also known as β-cat) in mice caused both morphologic and functional defects in motoneuron terminals of neuromuscular junctions (NMJs). In the absence of muscle β-catenin, acetylcholine receptor clusters were increased in size and distributed throughout a wider region. Primary nerve branches were mislocated, whereas secondary or intramuscular nerve branches were elongated and reduced in number. Both spontaneous and evoked neurotransmitter release was reduced at the mutant NMJs. Furthermore, short-term plasticity and calcium sensitivity of neurotransmitter release were compromised in β-catenin–deficient muscle. In contrast, the NMJ was normal in morphology and function in motoneuron-specific β-catenin–deficient mice. Taken together, these observations indicate a role for muscle β-catenin in presynaptic differentiation and function, identifying a previously unknown retrograde signaling in the synapse formation and synaptic plasticity.

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Figure 1: Phrenic nerve branch mislocation and enlarged central band of AChR clusters in HSA–β-cat−/− mice.
Figure 2: Characterization of postsynaptic differentiation in HSA–β-cat−/− mice.
Figure 3: Defective spontaneous ACh release in HSA–β-cat−/− NMJs.
Figure 4: Responsiveness of muscle fibers to exogenous cholinergic agonist CCh.
Figure 5: Impaired evoked ACh release in HSA–β-cat−/− NMJs.
Figure 6: Compromised short-term plasticity and calcium sensitivity in HSA–β-cat−/− NMJs.

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Acknowledgements

We are grateful to J. Melki and S. Arber for valuable mouse lines. This work was supported in part by grants from the US National Institutes of Health and the Muscular Dystrophy Association to L.M. and W.-C.X., National Natural Science Foundation of China (U0632007) and Program of Changjian Scholars and Innovative Research Team in University (IRT0731) to T.-M.G. T.-M.G. and L.M. are Chang Jiang Scholars.

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  1. Xiao-Ming Li and Xian-Ping Dong: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, 1120 15th Street, Augusta, 30912, Georgia, USA

    Xiao-Ming Li, Xian-Ping Dong, Shi-Wen Luo, Bin Zhang, Dae-Hoon Lee, Annie K L Ting, Hannah Neiswender, Chang-Hoon Kim, Ezekiel Carpenter-Hyland, Wen-Cheng Xiong & Lin Mei

  2. Department of Anatomy and Neurobiology, Southern Medical University, 1023 S Shatai Road, Guangzhou, 510515, China

    Xiao-Ming Li, Tian-Ming Gao & Lin Mei

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Li, XM., Dong, XP., Luo, SW. et al. Retrograde regulation of motoneuron differentiation by muscle β-catenin. Nat Neurosci 11, 262–268 (2008). https://doi.org/10.1038/nn2053

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