Table 1 |.

Summary of signals (ligands, receptors, cytoplasmic effectors and transcription factors) involved in sympathetic nervous system development

Process	Signal	Type	Description	Refs
Axon initiation/elongation	HGF/c-Met	Ligand/receptor	Neurite outgrowth in vitro	14,16
	Artemin/Ret/GFRα3	Ligand/receptor	Axon growth in vitro; aberrant axon projections in knockout mice in vivo	17,18
	NT3/TrkA	Ligand/receptor	Axon growth in vitro; impaired projections along intermediate targets in knockout mice in vivo	19,20
	Netrin/DCC	Ligand/receptor	Arterial innervation	21
	Endothelin 1/EdnrA	Ligand/receptor	Axon guidance	23
	Endothelin 3/EdnrA	Ligand/receptor	Axon pathway selection	25
	Sema3F	Ligand	Promotes growth cone collapse by antagonizing TrkA signalling in vitro	52
Target innervation	NGF/TrkA	Ligand/receptor	Axon growth, branching and growth cone responses in vitro; impaired target innervation in knockout mice in vivo	28,152,189,190
	Calcineurin	Phosphatase	Promotes axon growth by regulating dynamin 1 phosphorylation and TrkA endocytosis	34
	Rac1	Small GTPase	Axonal synthesis and prenylation promotes axon growth	38
	Tp53inp2	Axonal untranslated mRNA	Essential for NGF-mediated growth and target innervation	37
	CREB	Transcription factor	Axon growth defects in knockout mice	39
	Egr3	Transcription factor	Defects in target innervation in knockout mice	40
	Wnt5a/Ror1–2	Ligand/receptor	Autocrine signalling promotes axon branching in vitro; innervation defects in knockout mice in vivo	42,44,45
	CD40/CD40L	Ligand/receptor	Autocrine signalling regulates innervation of low-NGF-expressing targets	43
	GDF5	Ligand	Target-derived factor promotes innervation of select targets, independent of NGF	46
	TNFα/TNFR1	Ligand/receptor	Reverse signalling promotes axon growth and branching	47
	Cistn3β/S100b	ER-resident protein/soluble factor	Tissue-specific innervation of brown adipose tissue	48
	Sema3a/Nrp1/Plexin A4	Ligand/receptor/co-receptor	Defects in axon projections and cardiac innervation in knockout mice	23,50,191,192
Axon pruning	BDNF/p75	Ligand/receptor	Activity-dependent axon pruning via suppression of TrkA signalling	54,55
	DR6	Receptor	Axon pruning	55,57,58
Dendrite growth	NGF/TrkA	Ligand/receptor	Dendrite elaboration and maintenance	91,92
	Egr3	Transcription factor	Impaired dendrite elongation and branching in knockout mice in vivo	93
	α3 nAChR	Ion channel subunit	Loss of primary dendrites in knockout mice	100
	CaMKII/MEK/ILK	Kinases	Downstream effectors in activity-dependent dendrite growth	97,99
	BMP5, BMP6 and BMP7/Bmpr1a	Ligand/receptor	Promotes dendrite growth in vitro; perturbed dendrite growth in Bmpr1a knockout mice	101,102
	p75	Receptor	Necessary for BMP-induced dendrite maturation in vitro and in vivo	107
Synapse formation	BDNF/TrkB	Ligand/receptor	Increases synapse density by influencing preganglionic axon innervation	113
	NGF/TrkA	Ligand/receptor	Promotes synapse assembly in ganglia; increases synaptic contacts with peripheral targets and potentiates neurotransmitter release	64,65,94,95,112,193
	Agrin	Proteoglycan	Synapse stability	114
	α3 nAChR	Ion channel subunit	Excess synapse numbers, mis-localized synaptic contacts and impaired neurotransmission in knockout mice	100,119
Neuron survival	NGF/TrkA	Ligand/receptor	Loss of sympathetic neurons in knockout mice in vivo; NGF on distal axons promotes survival by retrograde TrkA signalling in compartmentalized cultures	27,71,72,194
	PI-3K/Akt	Kinases	Effector in retrograde TrkA trafficking and survival	195
	CREB	Transcription factor	Loss of sympathetic neurons in knockout mice in vivo and in vitro; promotes expression of pro-survival genes	39,77,196
	Egr3	Transcription factor	Neuron loss in knockout mice	40
	JNK	Kinase	Retrograde transport of apoptotic signals	83,85
	c-Jun	Transcription factor	Pro-apoptotic nuclear signalling	84
	BDNF/p75	Ligand/receptor	Pro-apoptotic signalling	41,82,83
	Pro-neurotrophins	Ligands	Pro-apoptotic signalling	86,87
Neuronal diversity	Hmx1	Transcription factor	Specification of adrenergic fate in precursors	124
	TrkC/Ret	Receptors	Specification of cholinergic fate in precursors	124
	LIF/CNTF	Ligands	Exogenous application or overexpression induces neurotransmitter switch in target innervation; no phenotypes observed in knockout mice	132,134–137
	Artemin/neurturin/Ret/GFRα1/GFRα3	Ligand/receptor/co-receptor	Postnatal specialization of noradrenergic subtypes upon target innervation	10

BDNF, brain-derived neurotrophic factor; BMP, bone morphogenetic protein; Clstn3, calsyntenin 3α; CNTF, ciliary neurotrophic factor; Egr3, early growth response 3; ER, endoplasmic reticulum; GDF, growth differentiation factor 5; HGF, hepatocyte growth factor; ILK, integrin-linked kinase; JNK, Jun-N-terminal kinase; LIF, leukaemia inhibitory factor; nAChR, nicotinic acetylcholine receptor; NGF, nerve growth factor.