TY - JOUR
T1 - Β-Catenin stabilization in skeletal muscles, but not in motor neurons, leads to aberrant motor innervation of the muscle during neuromuscular development in mice
AU - Liu, Yun
AU - Sugiura, Yoshie
AU - Wu, Fenfen
AU - Mi, Wentao
AU - Taketo, Makoto M.
AU - Cannon, Steve
AU - Carroll, Thomas
AU - Lin, Weichun
N1 - Funding Information:
We thank Dr. Eric Olson and Dr. Rhonda Bassel-Duby (UT Southwestern Medical Center) for providing Myo-Cre mice. This work was supported by Grants (to W. Lin) from NIH/NINDS ( NS055028, NS055028-03S1 ), the Edward Mallinckrodt, Jr. Scholar Program and the Cain Foundation in Medical Research .
PY - 2012/6/15
Y1 - 2012/6/15
N2 - Β-Catenin, a key component of the Wnt signaling pathway, has been implicated in the development of the neuromuscular junction (NMJ) in mice, but its precise role in this process remains unclear. Here we use a Β-catenin gain-of-function mouse model to stabilize Β-catenin selectively in either skeletal muscles or motor neurons. We found that Β-catenin stabilization in skeletal muscles resulted in increased motor axon number and excessive intramuscular nerve defasciculation and branching. In contrast, Β-catenin stabilization in motor neurons had no adverse effect on motor innervation pattern. Furthermore, stabilization of Β-catenin, either in skeletal muscles or in motor neurons, had no adverse effect on the formation and function of the NMJ. Our findings demonstrate that Β-catenin levels in developing muscles in mice are crucial for proper muscle innervation, rather than specifically affecting synapse formation at the NMJ, and that the regulation of muscle innervation by Β-catenin is mediated by a non-cell autonomous mechanism.
AB - Β-Catenin, a key component of the Wnt signaling pathway, has been implicated in the development of the neuromuscular junction (NMJ) in mice, but its precise role in this process remains unclear. Here we use a Β-catenin gain-of-function mouse model to stabilize Β-catenin selectively in either skeletal muscles or motor neurons. We found that Β-catenin stabilization in skeletal muscles resulted in increased motor axon number and excessive intramuscular nerve defasciculation and branching. In contrast, Β-catenin stabilization in motor neurons had no adverse effect on motor innervation pattern. Furthermore, stabilization of Β-catenin, either in skeletal muscles or in motor neurons, had no adverse effect on the formation and function of the NMJ. Our findings demonstrate that Β-catenin levels in developing muscles in mice are crucial for proper muscle innervation, rather than specifically affecting synapse formation at the NMJ, and that the regulation of muscle innervation by Β-catenin is mediated by a non-cell autonomous mechanism.
KW - Acetylcholine receptor
KW - Mouse genetics
KW - Nerve defasciculation
KW - Neuromuscular junction
KW - Synaptic transmission
UR - http://www.scopus.com/inward/record.url?scp=84861223632&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861223632&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2012.04.003
DO - 10.1016/j.ydbio.2012.04.003
M3 - Article
C2 - 22537499
AN - SCOPUS:84861223632
SN - 0012-1606
VL - 366
SP - 255
EP - 267
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -