Wade A. Grow, Ph.D.

Professor and Chair of Anatomy


 

Midwestern University
Arizona College of Osteopathic Medicine
Department of Anatomy
Agave #201B
19555 N. 59th Ave
Glendale, AZ 85308

Office: (623) 572-3686
e-mail: wgrowx@midwestern.edu

EDUCATION

B.S. Zoology University of Idaho 1985
Ph.D. Zoology University of Idaho 1994
Post-doctoral Developmental Neuroscience University of Arizona 1995-1998

RESEARCH SUMMARY

Area of interest:

Neuromuscular synapse formation.

We use the C2C12 skeletal muscle cell culture model to ask questions about muscle development and neuromuscular synapse formation.  C2C12 myoblasts proliferate in growth medium, but when switched to differentiation medium they fuse to form multinucleated myotubes. Specifically we are interested in developmental events on the postsynaptic side of the synapse.  One of the methods we use to assess normal development is the clustering of acetylcholine receptors (AChRs), and the signaling events that precede clustering.  AChRs are initially located throughout the plasma membrane but aggregate spontaneously into clusters as myotubes form.  The frequency of AChR clusters is increased in cell culture by the addition of motor neuron derived agrin, which activates the agrin signaling pathway.  Experiments that enhance or disrupt agrin-induced AChR clustering have led to a better understanding of muscle development and neuromuscular synapse formation.

Research projects:

Project I:

Role of myogenic regulatory factors in neuromuscular synapse formation.
Muscle development is guided by myogenic regulatory factors including MyoD and myogenin.  Our lab has used immunofluorescence to confirm the in vivo expression pattern of MyoD and myogenin in C2C12 cell culture.  MyoD expression is elevated while myoblasts are in growth medium, but myogenin expression is elevated when myoblasts are switched to differentiation medium.  Moreover, antibodies to MyoD or myogenin decrease the frequency of agrin-induced AChR clustering, and antibodies to MyoD decrease myogenin expression.  

Project II:

Role of myostatin in neuromuscular synapse formation.
Myostatin (growth differentiation factor 8, GDF8) inhibits myogenesis and is a potential therapeutic target for muscular dystrophy and other myopathies.  Animals with mutations in myostatin genes have increased muscle mass resulting from hypertrophy and hyperplasia.  Our lab has examined several myostatin inhibitors and determined that they may decrease the frequency of agrin-induced AChR clustering, as well as affect the expression pattern of MyoD or myogenin.

Project III:

C2C12 cell culture as a bioassay for environmental toxins.
Our lab has a long history of using the C2C12 cell culture model to assess potential environmental toxins.  Bioassays measure the frequency of agrin-induced AChR clustering and activation of the agrin signaling pathway.  We have surveyed several environmental toxins with the following published results: (1) Mercury decreases the frequency of agrin-induced but not spontaneous AChR clustering, (2) Nicotine decreases agrin signaling and AChR clustering, (3) The pesticide methoxylchlor decreases myotube formation by slowing myoblast proliferation, (4) Caffeine decreases AChR clustering, (5) Ethanol decreases agrin-induced AChR clustering, and (6) Plastic additives decrease agrin-induced AChR clustering and myotube formation.

Publications:

Jarosz J, White C, Grow WA. (2016) Sodium nitrate decreases agrin-induced acetylcholine receptor clustering. BMC Pharmacology and Toxicology 17:20.
DOI 10.1186/s40360-016-0062-0

Neufeld K, Ezell K, Grow WA. (2015) Plastic additives decrease agrin-induced acetylcholine receptor clusters and myotube formation in C2C12 skeletal muscle cell culture. CellBio 4:12-22.

Ball MK, Campbell DH, Ezell K, Henley JB, Standley PR, Grow WA. (2013) Antibody to MyoD or myogenin decreases acetylcholine receptor clustering in C2C12 myotube culture. CellBio 2:138-148.

Owen DB, Chamberlain KT, Shishido S, Grow WA. (2010) Ethanol decreases agrin-induced acetylcholine receptor clustering in C2C12 myotube culture. Toxicology in Vitro 24:645-651. 

Kordosky-Herrera K, Grow WA. (2009) Caffeine and nicotine decrease acetylcholine receptor clustering in C2C12 myotube culture. Cell & Tissue Res 335:341-348.

Steffens BW, Batia LM, Baarson CJ, Choi CKC, Grow WA. (2007) The pesticide methoxychlor decreases myotube formation in cell culture by slowing myoblast proliferation.  Toxicology in Vitro 21:770-781.

McDonnell KMW, Grow WA. (2004) Reduced glycosaminoglycan sulfation diminishes the agrin signal transduction pathway. Dev Neurosci 26:1-10.

Ferayorni AJ, Gunville CF, Grow WA. (2004) Nicotine decreases agrin signaling and acetylcholine receptor clustering in C2C12 myotube culture. J Neurobiol 60:51-60.

Miller T, Grow WA. (2004) Mercury decreases the frequency of induced but not spontaneous clustering of acetylcholine receptors. Cell & Tissue Res 316:211-219.

Grow WA, Eroschenko VP. (2002) The pesticide methoxychlor disrupts the fusion of myoblasts into myotubes in skeletal muscle cell culture. Toxicol Appl Pharmacol  179(2):105-110.

Grow WA, Gordon H. (2000) Sialic acid inhibits agrin signaling in C2 myotubes. Cell & Tissue Res  299(2):273-279.

Grow WA, Gordon H. (2000) Acetylcholine receptors are required for postsynaptic aggregation driven by the agrin signaling pathway. Eur J Neurosci  12(2):467-472.

Grow WA, Ferns M, Gordon H. (1999) A mechanism for acetylcholine receptorclustering distinct from agrin signaling. Dev Neurosci  21(6):436-443.

Grow WA, Ferns M, Gordon H. (1999) Agrin-independent activation of the agrin signal transduction pathway. J Neurobiol  40(3):356-365.

Grow WA, Kendall-Wassmuth E, Grober MS, Ulibarri C, Laskowski MB. (1996) Muscle fiber   type correlates with innervation topography in the rat serratus anterior muscle. Muscle & Nerve  19:605-613.

Grow WA, Kendall-Wassmuth E, Ulibarri C, Laskowski MB. (1995) Differential delay of reinnervating axons alters specificity in the rat serratus anterior muscle. J Neurobiol  26(4):553-562.