title: The p53 Pathway Controls SOX2-Mediated Reprogramming in the Adult Mouse Spinal Cord.
abstract: Although the adult mammalian spinal cord lacks intrinsic neurogenic capacity, glial cells can be reprogrammed in vivo to generate neurons after spinal cord injury (SCI). How this reprogramming process is molecularly regulated, however, is not clear. Through a series of in vivo screens, we show here that the p53-dependent pathway constitutes a critical checkpoint for SOX2-mediated reprogramming of resident glial cells in the adult mouse spinal cord. While it has no effect on the reprogramming efficiency, the p53 pathway promotes cell-cycle exit of SOX2-induced adult neuroblasts (iANBs). As such, silencing of either p53 or p21 markedly boosts the overall production of iANBs. A neurotrophic milieu supported by BDNF and NOG can robustly enhance maturation of these iANBs into diverse but predominantly glutamatergic neurons. Together, these findings have uncovered critical molecular and cellular checkpoints that may be manipulated to boost neuron regeneration after SCI.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai 200433, China. Electronic address: suzhida@smmu.edu.cn.
authors.forename: Zhida
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Tai
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xu
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: chun-li.zhang@utsouthwestern.edu.
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Zhang
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D065150:Cellular Reprogramming; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D055748:SOXB1 Transcription Factors; D016159:Tumor Suppressor Protein p53
keywords: BDNF; SOX2; adult neurogenesis; in vivo reprogramming; neural progenitors; neural regeneration; noggin; p21; p53; spinal cord injury