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Waking up the sleepers: shared transcriptional pathways in axonal regeneration and neurogenesis

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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.

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Abbreviations

AKT:

Protein kinase B

ATF3:

Cyclic AMP-dependent transcription factor

BDNF:

Brain-derived neurotrophic factor

BMPs:

Bone morphogenic proteins

cAMP:

Cyclic adenosine monophosphate

cGKI:

Cyclic guanosine monophosphate kinase I

CBP:

CREB binding protein

CNS:

Central nervous system

CNTF:

Ciliary neurotrophic factor

CREB:

cAMP response element-binding protein

CXCL12:

Chemokine (C-X-C motif) ligand 12

DRG:

Dorsal root ganglia

DYRK:

Dual-specificity tyrosine-regulated kinases

FGF:

Fibroblast growth factor

GABA:

Gamma-aminobutyric acid

GAP-43:

Growth associated protein 43

GDNF:

Glial-derived neurotrophic factor

GFAP:

Glial fibrillary acidic protein

GSK:

Glycogen synthase kinase

HDACs:

Histone deacetylases

Hes5:

Hairy and enhancer of split 5

IL6:

Interleukin 6

iPSCs:

Induced pluripotent stem cells

JNK:

c-Jun N-terminal kinases

KLF4:

Krüppel-like factor 4

LIF:

Leukemia inhibitory factor

MAPK:

Mitogen-activated protein kinase

MCP-1:

Monocyte chemotactic protein-1

NSCs:

Neural stem cells

NFAT:

Nuclear factor of activated T-cells

NGF:

Nerve growth factor

PCAF:

P300/CBP-associated factor

PKA:

Protein kinase A

PI3K:

Phosphoinositide 3-kinase

PSA-NCAM:

Polysialylated-neural cell adhesion molecule

PTEN:

Phosphatase and tensin homolog

Oct4:

Octamer binding transcription factor 4

Rab13:

Ras-related protein Rab-13

RAGs:

Regeneration associated genes

RhoA:

Ras homolog gene family, member A

RGC:

Retinal ganglion cells

RMS:

Rostral migratory stream

SGZ:

Subgranular zone

Shh:

Sonic hedgehog homolog

Smad:

Mothers against decapentaplegic homolog 1

SPRR1:

Small proline-rich protein 1

Sox:

Sry sex determining region Y (SRY)-related HMG box

STAT3:

Signal transducer and activator of transcription 3

SVZ:

Subventricular zone

TGFß:

Transforming growth factor beta

Trk:

Tropomyosin-receptor-kinase

Trp53:

Transformation related protein 53

VEGF:

Vascular endothelial growth factor

WNT:

Wingless-type MMTV integration site family, member 1

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Acknowledgments

This work was supported by funds granted by the Hertie Foundation; the Center for Integrative Neuroscience (CIN), University of Tuebingen; the DFG (all granted to Simone Di Giovanni).

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  1. Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Otfried-Mueller Strasse 27, 72076, Tuebingen, Germany

    Giorgia Quadrato & Simone Di Giovanni

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Correspondence to Giorgia Quadrato or Simone Di Giovanni.

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Quadrato, G., Di Giovanni, S. Waking up the sleepers: shared transcriptional pathways in axonal regeneration and neurogenesis. Cell. Mol. Life Sci. 70, 993–1007 (2013). https://doi.org/10.1007/s00018-012-1099-x

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  • DOI: https://doi.org/10.1007/s00018-012-1099-x

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