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Young-Jin Son, Ph.D.

Assistant Professor

Developmental Neurobiology

Office: 215-991-8274

Lab: 215-991-8471

Fax: 215-843-9082

Email: yson@drexelmed.edu

Plasticity and Repair of Synaptic Connections in Muscle and Spinal Cord

Neurons communicate with each other through specialized contacts called synapses, whose formation and maintenance are essential for proper functioning of the nervous system. Disturbance of synaptic connections by physical or pathological processes could be devastating. Our nervous system however has evolved ways to cope with such perturbations. In muscle, uninjured motoneurons sprout new axons and reestablish synaptic connections on inactive muscle fibers, restoring muscle function and strength. Limited but substantial plasticity of synaptic circuits with compensatory recovery has also been demonstrated in injured spinal cord. Our research goal is to clarify the features of structural plasticity of synaptic connections in muscle and spinal cord, to elucidate the molecular and cellular mechanisms responsible for extensive or limited plasticity of adult synapses, and to use the knowledge to promote functional repair of damaged synaptic connections. We use various molecular and cellular techniques, including transgenic mice and state-of-the art tools and techniques such as in vivo time-lapse imaging. We hope that the work will lead to novel insights into the roles played by glial cells at synapses, to increased understanding of the pathogenesis of neuronal and muscular diseases, and to the development of therapeutic strategies to repair synaptic connections in central and peripheral nervous systems. 

Current Research Projects

1. Compensatory sprouting of motor nerve terminals.  

Paralysis or partial denervation of adult vertebrate muscles elicits axonal sprouting of intact motor nerve terminals, a process termed ‘terminal sprouting’. Terminal sprouting restores functional innervation on denervated muscle fibers, contributing to substantial spontaneous and adaptive recovery of motor function after peripheral nerve injury and perhaps also after spinal cord injury. While numerous molecules have been implicated, the molecular and cellular events leading to the compensatory sprouting remain incompletely understood. Therapeutic efforts to promote motor recovery by enhancing compensatory sprouting are therefore limited. We investigate the molecular mechanisms responsible for the induction of terminal sprouting, with particular emphasis on the reactivation process of terminal Schwann cells which is thought to be essential for the maintenance and compensatory reestablishment of neuromuscular synapses in adults.

2. Stability and plasticity of neuromuscular synapses paralyzed by spinal cord injury 

Neuromuscular junctions are the ultimate relays of brain- and spinal cord-driven motor information to muscles. While stability and plasticity of these connections between nerve and muscle may influence motor deficits and subsequent recovery of motor function from spinal cord injury (SCI), surprisingly little attention has been given to SCI-evoked NMJ changes. We investigate the extent of anatomical denervation at the neuromuscular junctions caudal to SCI, understand the factors and conditions that affect stability of nerve-muscle connections after SCI and develop treatments that will maximize functional and anatomical integrity of neuromuscular junctions after SCI.

3. Axonal plasticity of injured or spared neurons in PNS and CNS

Intraspinal regeneration of adult sensory axons is primarily impeded at the dorsal root entry zone (DREZ), the interface between the CNS and PNS, but the mechanisms remain unclear. Applying time-lapse in vivo imaging and transgenic mouse lines expressing a spectral variant of GFP in subsets of neurons, we investigate naturally occurring processes of regeneration or sprouting of injured sensory neurons in vivo, to address fundamental questions such as, what are the cellular interactions between neurons and their environment that allow regeneration to succeed in the peripheral nervous system and why do damaged neurons fail to regenerate within the spinal cord?

Biography

Young-Jin Son received his B.Sc. degree in Biology from the Korea University and his Ph.D. degree from the University of Texas at Austin in 1994, where he worked with Wesley J. Thompson. Before joining the faculty of MCP Hahnemann in 2000, he obtained postdoctoral training first with Robert W. Wilkinson and Joshua R. Sanes at the Washington University in St. Louis, and then with Steven S. Carlson at the University of Washington in Seattle. 

Selected Publications

Megan Wright, Wha-Ja Cho, and Young-Jin Son  (2007) Distinct patterns of motor nerve terminal sprouting induced by Ciliary neurotrophic factor vs. Botulinum toxin. J. Comp. Neurol., in press *cover illustration

Hyuno Kang, Le Tian, Young-Jin Son, Yi Zuo, Diane Kopp, Flora Love, Christopher Hayworth, Joshua Trachtenberg, Michelle Mikesh, Lee Sutton, Olga Ponomareva, John Mignone, Grigori Enikolopov, Mendell Rimer and Wesley Thompson  (2007) Regulation of the intermediate filament protein nestin at rodent neuromuscular junctions by innervation and activity. J. Neurosci. 27:5948-5957 

Megan Wright and Young-Jin Son  (2007) Ciliary neurotrophic factor is not required for terminal sprouting and compensatory reinnervation of neuromuscular synapses: Re-evaluation of CNTF null mice. Exp. Neurol. 205:437-448

Anthony S. Burns, Sabiha Jawaid, Hui Zhong, Hiroyuki Yoshihara, Srishti Bhagat, Marion Murray, Roland R. Roy, Alan Tessler and Young-Jin Son   (2007) Paralysis elicited by spinal cord injury evokes selective disassembly of neuromuscular synapses with and without terminal sprouting in ankle flexors of the adult rat. J. Comp. Neurol. 500:116-33.

Love FM, Son YJ, Thompson, WJ (2003) Activity alters muscle reinnervation and terminal sprouting by reducing the number of Schwann cell pathways that grow to link synaptic sites. J. Neurobiol. 54:566- 576.

Son YJ, Scranton TW, Sunderland WJ, Baek SJ, Miner JH, Sanes JR, Carlson SS (2000) The synaptic vesicle protein SV2 is complexed with an alpha5-containing laminin on the nerve terminal surface. J. Biol. Chem. 275:451-60.

Son YJ, Patton BL, Sanes JR. (1999) Induction of presynaptic differentiation in cultured neurons by extracellular matrix components. Eur. J. Neurosci. 11:3457-67.

Wilkinson RS, Son YJ, Lunin SD (1996)  Release properties of isolated neuromuscular boutons of the garter snake.  J. Physiol (London)  495.2:503-514

Son YJ, Trachtenberg JT, Thompson WJ (1996) Schwann cells induce and guide sprouting and reinnervation of neuromuscular junctions. Trends. Neurosci. 19:280-285

Son YJ, Thompson WJ (1995) Nerve sprouting in muscle is induced and guided by processes extended by Schwann cells.  Neuron 14:133-141

Son YJ,Thompson WJ (1995) Schwann cell processes guide regeneration of peripheral axons. Neuron 14:125-132

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