Editing Synaptogenesis (section)

=== Signaling molecules ===

==== UNC-4 transcription factor ====
What specific molecules and chemical signals are involved in synaptogenesis has yet to be fully understood. Some evidence posits that [[Transcription factor|transcription factors]] are heavily involved in directing where axons and dendrites form synapses before and after synaptogenesis. The main study focusing on this involved motor neurons of ''[[Caenorhabditis elegans|C.elegans]]''. In this study, researchers found that knockout animals without the gene, ''unc-4'' have motor defects specifically with moving backwards. This gene is necessary for the Prd-like homeodomain transcription factor. These animals also had abnormal synaptic specificity indicating that this transcription factor is likely involved in determining where and how synapses are formed.<ref>{{cite journal | vauthors = Von Stetina SE, Treinin M, Miller DM | title = The motor circuit | journal = International Review of Neurobiology | volume = 69 | pages = 125–167 | date = 2005 | pmid = 16492464 | doi = 10.1016/s0074-7742(05)69005-8 | publisher = Elsevier | isbn = 978-0-12-366870-7 }}</ref>

Other studies found that this transcription factor was involved in synaptic strength. In this study, it was found that the u''nc-4'' pathway negatively regulates ''ceh-12'', a gene involved in regulating synaptic choice.<ref>{{cite journal | vauthors = Von Stetina SE, Fox RM, Watkins KL, Starich TA, Shaw JE, Miller DM | title = UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans | journal = Genes & Development | volume = 21 | issue = 3 | pages = 332–346 | date = February 2007 | pmid = 17289921 | pmc = 1785118 | doi = 10.1101/gad.1502107 }}</ref>

==== 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>