title: 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.affiliation: Kentucky Spinal Cord Injury Research Center, Department of Neurological Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA. yupanpan21@163.com
authors.forename: Panpan
authors.initials: P
authors.lastname: Yu
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Zhang
authors.forename: Lisa B E
authors.initials: LB
authors.lastname: Shields
authors.forename: Yiyan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Hu
authors.forename: Rachel
authors.initials: R
authors.lastname: Hill
authors.forename: Russell
authors.initials: R
authors.lastname: Howard
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gu
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Burke
authors.forename: Scott R
authors.initials: SR
authors.lastname: Whittemore
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xu
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Shields
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2