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First published online 31 January 2007
doi: 10.1242/dev.02783

Development 134, 901-908 (2007)
Published by The Company of Biologists 2007
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Syne-1 and Syne-2 play crucial roles in myonuclear anchorage and motor neuron innervation

Xiaochang Zhang1, Rener Xu1,*, Binggen Zhu1, Xiujuan Yang2, Xu Ding1, Shumin Duan2, Tian Xu1,3, Yuan Zhuang1,4 and Min Han1,5

1 Institute of Developmental Biology and Molecular Medicine, School of Life Science, Fudan University, Shanghai, 200433, China.
2 Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
3 Howard Hughes Medical Institute and Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
4 Department of Immunology, Duke University Medical Center, Durham, NC 27706, USA.
5 Howard Hughes Medical Institute and Department of MCDB, University of Colorado, Boulder, CO 80309, USA.

* Author for correspondence (e-mail: rener_xu{at}fudan.edu.cn)

Accepted 14 December 2006

Proper nuclear positioning is important to cell function in many biological processes during animal development. In certain cells, the KASH-domain-containing proteins have been shown to be associated with the nuclear envelope, and to be involved in both nuclear anchorage and migration. We investigated the mechanism and function of nuclear anchorage in skeletal muscle cells by generating mice with single and double-disruption of the KASH-domain-containing genes Syne1 (also known as Syne-1) and Syne2 (also known as Syne-2). We showed that the deletion of the KASH domain of Syne-1 abolished the formation of clusters of synaptic nuclei and disrupted the organization of non-synaptic nuclei in skeletal muscle. Further analysis indicated that the loss of synaptic nuclei in Syne-1 KASH-knockout mice significantly affected the innervation sites and caused longer motor nerve branches. Although disruption of neither Syne-1 nor Syne-2 affected viability or fertility, Syne-1; Syne-2 double-knockout mice died of respiratory failure within 20 minutes of birth. These results suggest that the KASH-domain-containing proteins Syne-1 and Syne-2 play crucial roles in anchoring both synaptic and non-synaptic myonuclei that are important for proper motor neuron innervation and respiration.

Key words: Synaptic nuclei, Neuromuscular junction, Neonatal lethality, Nuclear envelope, KASH, SUN domain, Nesprin, ANC-1, MSP-300, Mouse


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