Editing Synaptogenesis (section)

==== Growth cones and guidance cues ====
[[File:Growthcone.jpg|thumb|Image of axonal growth cones ]]
Guidance cues are essential for nervous system development as well as synaptic maintenance and remodeling.<ref name=":0">{{cite journal | vauthors = Yuasa-Kawada J, Kinoshita-Kawada M, Tsuboi Y, Wu JY | title = Neuronal guidance genes in health and diseases | journal = Protein & Cell | volume = 14 | issue = 4 | pages = 238–261 | date = April 2023 | pmid = 36942388 | pmc = 10121128 | doi = 10.1093/procel/pwac030 }}</ref> Guidance cues--attractive or repulsive--are sensed by growth cones. Expression of guidance cue genes is mediated at the transcriptional, post-transcriptional, translational, and post-translational levels. 

Most guidance cues converge onto various families of small GTPases which go back and forth from active to inactive forms. There are a multitude of signaling pathways involved in this process but the key ones involve netrins (NTNs) and fibronectin leucine-rich repeat transmembrane proteins (FLRTs), the ''Slit'' family, semamorphins (SEMA), [[ephrin]], non-canonical genes (morphogens, chemokines, growth factors), and RTN4 receptors.<ref name=":0" />

===== Netrin and FLRTs signaling pathways =====
NTNs and FLRTs both act as guidance cues. NTNs may act as attractants or repellents by DCC and neogenin1, or repellants by UNC5 receptors. UNC5s also act as repulsive receptors for FLRTs. Besides guidance cues, NTNs and FLRTs are also involved in synaptic specificity and synaptogenesis.<ref name=":0" />

In studying [[Netrin]], one study found that Netrin is not needed for long-range guidance decision, but is used for short-range synaptic targeting. This was determined from studying an RP3 axon, which expresses Netrin as an axonal guidance cue. In gene knockout studies of Netrin, the RP3 growth cone still formed the correct synapses but the connections were not strong.<ref>{{cite journal | vauthors = Mitchell KJ, Doyle JL, Serafini T, Kennedy TE, Tessier-Lavigne M, Goodman CS, Dickson BJ | title = Genetic analysis of Netrin genes in Drosophila: Netrins guide CNS commissural axons and peripheral motor axons | journal = Neuron | volume = 17 | issue = 2 | pages = 203–215 | date = August 1996 | pmid = 8780645 | doi = 10.1016/s0896-6273(00)80153-1 }}</ref>