gocentral
commented
11 years ago Hi Aleks,
Quoting PMID:17703212:
"Growth cone guidance during development, as well as axonal extension in neural repair and plasticity, is strongly regulated by both attractive (growth-promoting) and repulsive (growth-inhibiting) guidance molecules. The growth cone collapse assay has been widely and successfully used for the identification and purification of molecules that are repulsive to growth cones or inhibit axonal outgrowth. (...) Localized repellents can induce growth cones to turn away, but when a growth cone cannot escape a repellent stimulus, it loses its spread morphology and becomes temporarily paralyzed. This behavior is referred to as growth cone collapse. (...) Growth cone collapse serves as a very sensitive and reliable indicator of repellent activity."
Based on this, I'd be wary of adding a term for 'growth cone collapse' because this refers very much to an assay, and may not always be used to distinguish between the two occurrences of (negative) axon/dendrite guidance and (negative) regeneration. Actually, it seems to me that 'growth cone collapse', if anything, would relate more to 'guidance' than to 'regeneration' terms in GO, but this is not clear-cut, as is often with read-outs of assays, which may not be able to distinguish between different processes. Back to the sentence that says "The growth cone collapse assay has been widely and successfully used for the identification and purification of molecules that are repulsive to growth cones or inhibit axonal outgrowth", we have two separate processes described here:
1) "repulsive to growth cones" I would annotate to GO:NEW negative regulation of neuron projection extension involved in neuron projection guidance (would be is_a child of GO:1902284 neuron projection extension involved in neuron projection guidance; we already have analogous terms for axons)
2) "inhibit axonal outgrowth" I would annotate to GO:0070571 negative regulation of neuron projection regeneration
Thy-1 seems to fall into this two-annotation case, based on this sentence from PMID:22479590: "our data indicates that α(V)β(3) integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering."
If you agree with my comments, you may create GO:NEW 'negative regulation of neuron projection extension involved in neuron projection guidance' using TermGenie (you do have an account, right?), and I could add 'growth cone collapse' as a related synonym to both the new term and GO:0070571 'negative regulation of neuron projection regeneration'. Otherwise, I think we'd need further references to show that 'growth cone collapse' is used unambiguously to refer to only one of the two processes. Let me know what you think.
Thanks! Paola
Original comment by: paolaroncaglia
Hi, I am annotating a paper (PMID: 22479590) that describes the ability of rat/mouse Thy-1 (P01830 and P01831, respectively) to inhibit neurite outgrowth. In Fig. 4, 5 and 6 it is shown that this protein is expressed in growth cones and stimulation by its ligand alphaVbeta3-integrin-Fc induces retraction of axons and their collapse. We have a GO term GO:0070571 "negative regulation of neuron projection regeneration" with a definition "Any process that stops, prevents, or reduces the frequency, rate or extent of neuron projection regeneration, the regrowth of neuronal processes such as axons or dendrites following their loss or damage." According to the definition, this term refers to various types of axon outgrowth inhibition: it may be repulsion of axon growth, when axon just tends to avoid certain guidance cues but still grow and stay healthy or it may mean inhibition when axon is not able to grow and stops at a certain place. I would like to suggest a new term "growth cone collapse" which is often used in regenerative neuroscience and refers to the situation when axon is not just repelled or retracted but loses its growth cone motility. The main properties of growth cone collapse are well-described in literature, for example, in PMID: 17703212. The collapsed growth cones are known to lose filopodia and become round, as it is shown on Fig. 6D (PMID: 22479590). I think this term reflects better the observed axonal behavior. Thus, it is possible to show that Thy-1 may act as a neurite outgrowth inhibitor strong enough to cause growth cone collapse. This term can be a child of GO:0070571 "negative regulation of neuron projection regeneration". And a possible definition: Any process that causes loss of motile activity and cessation of advance by growth cones during the regrowth of neuronal processes such as axons or dendrites following their injury. Thanks, Aleks
Reported by: zebrafishembryo
Original Ticket: geneontology/ontology-requests/10267