Waking up the sleepers: shared transcriptional pathways in axonal regeneration and neurogenesis
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Cellular and Molecular Life Sciences
REVIEW
Waking up the sleepers: shared transcriptional pathways in axonal regeneration and neurogenesis Giorgia Quadrato • Simone Di Giovanni
Received: 20 March 2012 / Revised: 13 June 2012 / Accepted: 17 July 2012 / Published online: 17 August 2012 Ó Springer Basel AG 2012
Abstract In the last several years, relevant progress has been made in our understanding of the transcriptional machinery regulating CNS repair after acute injury, such as following trauma or stroke. In order to survive and functionally reconnect to the synaptic network, injured neurons activate an intrinsic rescue program aimed to increase their plasticity. Perhaps, in the attempt to switch back to a plastic and growth-competent state, post-mitotic neurons wake up and re-express a set of transcription factors that are also critical for the regulation of their younger brothers, the neural stem cells. Here, we review and discuss the transcriptional pathways regulating both axonal regeneration and neurogenesis highlighting the connection between the two. Clarification of their common molecular substrate may help simultaneous targeting of both neurogenesis and axonal regeneration with the hope to enhance functional recovery following CNS injury. Keywords Transcriptional program Synaptic network Neuronal plasticity Axonal regeneration Neurogenesis CNS repair Abbreviations AKT Protein kinase B ATF3 Cyclic AMP-dependent transcription factor BDNF Brain-derived neurotrophic factor
G. Quadrato (&) S. Di Giovanni (&) Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Otfried-Mueller Strasse 27, 72076 Tuebingen, Germany e-mail: [email protected] S. Di Giovanni e-mail: [email protected]
BMPs cAMP cGKI CBP CNS CNTF CREB CXCL12 DRG DYRK FGF GABA GAP-43 GDNF GFAP GSK HDACs Hes5 IL6 iPSCs JNK KLF4 LIF MAPK MCP-1 NSCs NFAT NGF PCAF PKA PI3K PSA-NCAM PTEN Oct4 Rab13
Bone morphogenic proteins Cyclic adenosine monophosphate Cyclic guanosine monophosphate kinase I CREB binding protein Central nervous system Ciliary neurotrophic factor cAMP response element-binding protein Chemokine (C-X-C motif) ligand 12 Dorsal root ganglia Dual-specificity tyrosine-regulated kinases Fibroblast growth factor Gamma-aminobutyric acid Growth associated protein 43 Glial-derived neurotrophic factor Glial fibrillary acidic protein Glycogen synthase kinase Histone deacetylases Hairy and enhancer of split 5 Interleukin 6 Induced pluripotent stem cells c-Jun N-terminal kinases Kru¨ppel-like factor 4 Leukemia inhibitory factor Mitogen-activated protein kinase Monocyte chemotactic protein-1 Neural stem cells Nuclear factor of activated T-cells Nerve growth factor P300/CBP-associated factor Protein kinase A Phosphoinositide 3-kinase Polysialylated-neural cell adhesion molecule Phosphatase and tensin homolog Octamer binding transcription factor 4 Ras-related protein Rab-13
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