Table 3. Comparison of Key Factors and Signallings During Axon Regeneration in C. elegans and Mammals.

Molecules	C. elegans	Mammals	References
Calcium
First signal	First signal induced by injury via activation of the voltage-gated Ca2+ channel current (EGL-19)	Activation of the L-type voltage-gated Ca2+ channel current triggers transcriptional changes promoting regrowth	Ghosh-Roy et al., 2010; Enes et al., 2010
Downstream effects	Downstream effects on growth cone formation	Control of growth cone formation
cAMP
Ca2+ dependence	Activated by Ca2+ transient increase and activation of specific adenyl cyclase	Ca2+ dependent increase	Ghosh-Roy et al., 2010; Park et al., 2004; Neumann et al., 2002; Spencer and Filbin, 2004
Ca2+ independent	Enhances axon regeneration	Enhances regeneration in rat sciatic nerve, in CNS and central branch of DRGs in presence of the myelin-associated inhibitors in vivo
PKA
Related to Ca2+ for regeneration	Promotes axonal regrowth, reconnection of distal and proximal axonal fragments, formation of branches to the target region	Regulation of cytoskeleton organization, inhibits Rho dependent inhibitory effects of myelin associated glycoprotein on regeneration	Ghosh-Roy et al., 2010; Snider et al., 2002
DLK-1
Key for axon regeneration	Promotes regrowth of C. elegans touch neurons and motor neurons	Promotes DRG neuron regrowth in culture	Hammarlund et al., 2009;
Involved in injury-dependent cytoskeleton remodelling	Activates microtubule dynamics for growth cone formation Crosstalks between the DLK-1 and the MLK-type MLK-1/KGB-1 JNK	Enhances an axonal retrograde injury signal (involving cytoskeleton) in peripheral nerves	Yan et al., 2009; Itoh et al., 2009; Shin et al., 2012;
	A mammalian DLK homolog rescues C. elegans axon regeneration in dlk-1 mutants in vivo	Activates c-JUN in DRG
DLK-1 independent pathway
Alternative regenerative pathway related	ASJ neurons: Triggered by reduced neuronal activity and improved by calcium and cAMP Activation of SAX-1/NDR kinase or UNC-43/CaMKII	Repair in DRG in CNS ranch after « lesion-conditioning »	Chung et al., 2016; Enes et al., 2010
DAF-18/PTEN mTOR
Negative regulator of regeneration	DAF-18/PTEN negatively regulates GABA motor neuron axon regeneration. PTEN’s function might be mediated via mTOR	PTEN is a negative mediator of axon regeneration of retinal ganglion cells, peripheral sensory (sciatic) neurons, corticospinal neurons via inhibition of mTOR	Byrne et al., 2014; Liu et al., 2010; Park et al., 2008
Daf-16/FOXO
Insulin pathway affects regeneration	DAF-2 (insulin receptor) dependent activation of DAF-16 regulates age-dependent inhibition of GABA motor neuron axon regeneration in parallel or upstream of DLK-1 pathway	IGF-1 (insulin growth factor) stimulates injured segment of rat sciatic nerve regeneration	Byrne et al., 2014; Sjoberg and Kanje, 1989
EFA-6
Microtubule-associated protein negatively regulating regeneration	Involved in MT dynamics Inhibition of regeneration	EFA6A, C, D expressed in neurons	Chen et al., 2011; Chen et al., 2015; Sakagami et al., 2006
PATRONIN-1
Microtubule associated protein promoting regeneration	Required for axon regrowth, modulating MT dynamics	Of the three mammalian CAMSAPs, CAMSAP2 is important for axon specification, dendrite morphology in mouse hippocampal neurons	Chuang et al., 2014; Yau et al., 2014
Nogo-A/Ret-1
Molecule of the niche negatively influencing axon regrow	Inhibition of sensitivity to Ephrin	Neurite inhibitory protein	Torpe et al., 2017; Freund et al., 2006
HIF-1
Stress pathway activated after injury for axon regrow	Axotomy in GABAergic D (non-serotonergic) neurons caused activation of hypoxia-inducible (HIF); this activates tph-1 (tryptophan hydrolase) expression and transient synthesis of serotonin which activates pro-regenerative pathways	Injury dependent activation of hypoxia-inducible (HIF) expression and targets Increased after spinal cord injury, increases protein stability and activates HIF-1α target genes	Alam et al., 2016; Xiaowei et al., 2006