Erna van Niekerk
During development, neurons extend axons throughout the nervous system, establishing connections with postsynaptic targets that are often located long distances away from their somata. The ability of these young neurons to robustly extend their axons is dramatically diminished in adulthood, and this reduced intrinsic growth capacity is a key mechanism underlying the inability of adult central nervous system (CNS) neurons to regenerate their axons following injury.
We focus primarily on the corticospinal (CST) system because it is the most important voluntary motor projection in humans and is especially refractory to regeneration attempts. Taking a large data approach to CST regeneration through RNA sequencing and proteomic efforts, our aim is to identify regeneration specific mechanisms that contribute to CST axon growth and augment these pathways and mechanisms in the adult CST following spinal cord injury.
Similarly, the corticospinal system contributes to fine motor control that is absent at birth in most mammals but gradually emerges during subsequent maturation of CST circuitry. The nature of circuit development and reorganization during this period remains largely unexplored. Utilizing RNA sequencing techniques we begin to identify the learning transcriptome of the CST to better understand what facilitates CST control of movement and what promotes sustained synaptic circuitry.
1. van Niekerk EA (2016). An Omic approach to Spinal Cord Injury Mechanisms. J Neurol Neuromed 1:37-39.
2. Wang L, Conner JM, Nagahara AH, Tuszynski MH. Rehabilitation drives enhancement of neuronal structure in functionally relevant neuronal subsets: Cholinergic dependence. Proc Nat Acad Sci, 2016; 115:2750-2755
3. Biane JS, Takashima Y, Conner JM, Massimo Scanziani, Tuszynski MH. Thalamocortical projections exhibit plasticity onto behaviorally-relevant neurons during adult motor learning. Neuron 2016; 89:1173-1179
4. Kota V, Sommer G, Durette C, Thibault P, van Niekerk EA, Twiss JL, Heise T (2016). SUMO-modification of the La Protein facilitates binding to mRNA in vitro and in cells. PLoS One. e0156365
5. van Niekerk EA, Tuszynski MH, Lu P, Dulin JN (2016). Molecular and Cellular Mechanisms of Axonal Regeneration after Spinal Cord Injury. Molecular and Cellular Proteomics. 15:394-408
6. van Niekerk E, Yoon C*, Henry K, Ishikawa T, Orita S, Tuszynski MH, Campana WM (2013). Low-density lipoprotein receptor-related protein 1 (LRP1)-dependent cell signaling promotes axonal regeneration. J Biol Chem. 288:26557-68. (*Yoon C and van Niekerk E contributed equally to this work).
7. Hou S, Nicholson L, van Niekerk E, Motsch M, Blesch A (2012). Dependence of regenerated sensory axons on continuous neurotrophin-3 delivery. J Neurosci, 32:13206-20.
8. Wang L, Conner JM, Rickert JL, Tuszynski MH. Structural plasticity within highly specific neuronal populations identifies a parcellation of motor learning. Proc Nat Acad Sci, 2011, 108:2545-2550.
9. van Niekerk EA, Yoo S*, Merianda TT, Twiss JL (2010). Dynamics of axonal mRNA transport and implications for peripheral nerve regeneration. Exp. Neurol. 223:19-27 (*van Niekerk E and Yoo S contributed equally to this work).
10. van Niekerk E, Willis DE, Chang JH, Heise T, Twiss JL (2007). Sumoylation in axons triggers retrograde transport of the RNA binding protein La. Proc. Natl. Acad Sci. USA 104:12913-18.
[This paper was featured in Nature Reviews Neuroscience 81: 656 (2007)].
11. Willis DE, van Niekerk E, Merianda TT, Williams GW, Kendall M, Twiss JL (2007). Extracellular stimuli specifically regulate transport of individual neuronal mRNAs. Journal of Cell Biol. 178:965-80.
[This paper was featured in Journal of Cell Biology 178:965-80]
12. Wang W, van Niekerk E, Willis DE, Twiss JL (2007). RNA transport and localized protein synthesis in neurological disorders and neural repair. Dev. Neurobiol. 67:1166-82.
13. Chang JH, Vuppalanchi D, van Niekerk E, Trepel JB, Schanen NC, Twiss JL (2006). PC12 cells regulate ICER expression to differentially control CRE-dependent transcription in response to NGF and cAMP. J Neurochemistry, 99:1517-30.
14. Conner JM, Chiba AA, Tuszynski MH. The basal forebrain cholinergic system is essential for cortical plasticity and functional recovery following brain injury. Neuron, 2005, 46:173-9.