Inhibitor of DNA binding 2 promotes sensory axonal growth after SCI.

Abstract

This study investigated whether neuronal inhibitor of DNA binding 2 (Id2), a regulator of basic helix-loop-helix (bHLH) transcription factors, can activate the intrinsic neuritogenetic mode of dorsal root ganglion (DRG) neurons in adult mice following spinal cord injury (SCI). First, the Id2 developmental expression profile of DRG neurons, along with the correlated activity of Cdh1-anaphase promoting complex (Cdh1-APC), was characterized. Next, a D-box mutant Id2 (Id2DBM) adenoviral vector, resistant to Cdh1-APC degradation, was developed to enhance neuronal Id2 expression. After the vector was introduced into DRG neurons, the effect of Id2 on neurite outgrowth of cultured DRG neurons and sensory axonal regeneration following spinal cord dorsal hemisection was evaluated. The expression of Id2 in DRG neurons was high in the embryonic stage, downregulated after birth, and significantly reduced in the adult. Expression of Cdh1-APC was opposite to Id2, which may be responsible for Id2 degradation during DRG maturation. Overexpression of Id2DBM in DRG neurons enhanced neuritogenesis on both permissive and inhibitory substrates. Following spinal cord dorsal hemisection, overexpression of Id2DBM reduced axon dieback and increased the number and length of regenerative fibers into the lesion gap. Reprogramming the intrinsic growth status of quiescent adult DRG neurons by enhancing Id2 expression results in active neuritogenesis following SCI. Id2 may be a novel target for enhancing sensory axonal regeneration following injuries to the adult spinal cord.

• Authors: Panpan Yu, Yi-Ping Zhang, Lisa B E Shields, Yiyan Zheng, Xiaoling Hu, Rachel Hill, Russell Howard, Zhen Gu, Darlene A Burke, Scott R Whittemore, Xiao-Ming Xu, Christopher B Shields
• Journal: Experimental neurology (Exp Neurol) Vol. 231 Issue 1 Pg. 38-44 (Sep 2011) ISSN: 1090-2430 [Electronic] United States
• PMID: 21679705 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011. Published by Elsevier Inc.

Chemical References

• Idb2 protein, mouse
• Inhibitor of Differentiation Protein 2

Topics

• Animals
• Animals, Newborn
• Cells, Cultured
• Disease Models, Animal
• Female
• Ganglia, Spinal (embryology, growth & development, metabolism)
• Gene Targeting (methods)
• Genetic Therapy (methods)
• Growth Cones (metabolism, ultrastructure)
• Inhibitor of Differentiation Protein 2 (genetics, metabolism, physiology)
• Mice
• Mice, Inbred C57BL
• Nerve Regeneration (genetics, physiology)
• Sensory Receptor Cells (cytology, metabolism)
• Spinal Cord Injuries (physiopathology, therapy)
• Treatment Outcome