- Chandran, Vijayendran;
- Coppola, Giovanni;
- Nawabi, Homaira;
- Omura, Takao;
- Versano, Revital;
- Huebner, Eric A;
- Zhang, Alice;
- Costigan, Michael;
- Yekkirala, Ajay;
- Barrett, Lee;
- Blesch, Armin;
- Michaelevski, Izhak;
- Davis-Turak, Jeremy;
- Gao, Fuying;
- Langfelder, Peter;
- Horvath, Steve;
- He, Zhigang;
- Benowitz, Larry;
- Fainzilber, Mike;
- Tuszynski, Mark;
- Woolf, Clifford J;
- Geschwind, Daniel H
The regenerative capacity of the injured CNS in adult mammals is severely limited, yet axons in the peripheral nervous system (PNS) regrow, albeit to a limited extent, after injury. We reasoned that coordinate regulation of gene expression in injured neurons involving multiple pathways was central to PNS regenerative capacity. To provide a framework for revealing pathways involved in PNS axon regrowth after injury, we applied a comprehensive systems biology approach, starting with gene expression profiling of dorsal root ganglia (DRGs) combined with multi-level bioinformatic analyses and experimental validation of network predictions. We used this rubric to identify a drug that accelerates DRG neurite outgrowth in vitro and optic nerve outgrowth in vivo by inducing elements of the identified network. The work provides a functional genomics foundation for understanding neural repair and proof of the power of such approaches in tackling complex problems in nervous system biology.