"germ cell migration" (GO:0008354) - issues with term name, equivalence axiom, synonyms

[krchristie]

These two papers talk about the role of Lypd4, Pdilt, and several additional proteins having a role in maturation of Adam3, a sperm cell surface protein that is essential for "migration of sperm from uterus to oviduct". Mutations in these genes in mice do NOT have any effect of "flagellated sperm motility".

• Wang D, et al. LYPD4, mouse homolog of a human acrosome protein, is essential for sperm fertilizing ability and male fertility. Biol Reprod. 2020 Apr 24;102(5):1033-1044. PMID: 32040177.

• Tokuhiro K, et al. Protein disulfide isomerase homolog PDILT is required for quality control of sperm membrane protein ADAM3 and male fertility [corrected]. Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3850-5. PMID: 22357757

Looking in Noctua, I see that the curator actually chose the term "cell migration", but that the logic over the GO term, extensions, and relationships has come up with the term "germ cell migration":

However, the definition of the term "germ cell migration" (stanza included below) is very clearly talking about the migration of embryonic/primordial germ cells within the embryo to move to the location where the gonads are developing. This is clearly a very different "germ cell migration" from "migration of sperm from uterus to oviduct" and has nothing to do with the movement of sperm cells within the female reproductive tract.

Via some Google and PubMed searches, I think we need to make some modifications to this term.

Some interesting PubMed search results for quoted strings:

• "embryonic germ cell migration" - 762
• "primordial germ cell migration" - 102
• "pole cell migration" - 6 (here are the years: 1995, 1996, 1998, 1999, 2004, 2012)
• "germ cell migration" = "germ-cell migration" - 261 ** 347 instances of "germ cell" vs 11 instances of "germ-cell" in first 200 citations

Three good reviews:

• Grimaldi C, Raz E. Germ cell migration-Evolutionary issues and current understanding. Semin Cell Dev Biol. 2020 Apr;100:152-159. PMID: 31864795.
• Barton LJ, LeBlanc MG, Lehmann R. Finding their way: themes in germ cell migration. Curr Opin Cell Biol. 2016 Oct;42:128-137. PMID: 27484857
• Richardson BE, Lehmann R. Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nat Rev Mol Cell Biol. 2010 Jan;11(1):37-49. PMID: 20027186

Here is the current stanza:

id: GO:0008354 name: germ cell migration namespace: biological_process def: "The orderly movement of a cell specialized to produce haploid gametes through the embryo from its site of production to the place where the gonads will form." [GOC:bf, GOC:jl] synonym: "germ-cell migration" EXACT [] synonym: "primordial germ cell migration" RELATED [] is_a: GO:0016477 ! cell migration intersection_of: GO:0016477 ! cell migration intersection_of: results_in_movement_of CL:0000586 ! germ cell relationship: part_of GO:0007276 ! gamete generation

Proposed changes:

• name: germ cell migration => embryonic germ cell migration
• def: "The orderly movement of a cell specialized to produce haploid gametes through the embryo from its site of production to the place where the gonads will form." [GOC:bf, GOC:jl] => add the three PMID's above
• synonym: "germ-cell migration" EXACT [] => "embryonic germ-cell migration"
• synonym: "primordial germ cell migration" RELATED [] => change to EXACT
• intersection_of: results_in_movement_of CL:0000586 ! germ cell => primordial germ cell ! CL:0000670

[pgaudet]

@krchristie are you sure this will be OK for all existing annotations? or should we create 2 children?

[krchristie]

Hi @pgaudet

With the definition that "germ cell migration" has:

def: "The orderly movement of a cell specialized to produce haploid gametes through the embryo from its site of production to the place where the gonads will form." [GOC:bf, GOC:jl]

it is clear that it should only have meant "embryonic germ cell migration".

I took a look at how it has been used. Here are the results:

I didn't count the MGI two annotations that initiated this ticket in the total for "germ cell migration" because the curator (@ukemi) actually chose the term "cell migration" with the extension _occursin "oviduct", and the reasoning in Noctua over a couple incorrect relationships in the ontology is generating the term "germ cell migration".

Of the annotations made directly to "germ cell migration", over 90% are using the term correctly.

Here's a breakdown of the papers the remaining 6 annotations were made from:

• 1 C. elegans paper describing "gonad migration" - This one might be fine, but I don't know anything about germ cell or gonad migration in C elegans, so it would be great if @vanaukenk could comment on this.
• 2 papers (1 mouse & 1 rat) talking about "neonatal gonocyte migration to basal lamina within testis"
• 1 paper talking about "migration of germ cells across the blood-testis barrier during spermatogenesis"
• 2 papers (1 curated by AgBase & 1 by FlyBase) where I have no idea why the term "germ cell migration" was chosen

Considering how few annotations are NOT supposed to be "embryonic primordial germ cell migration", I think it would be best to consider the other annotations mistakes and just correct those since they clearly don't match the definition of the term "germ cell migration".

If you do not feel that you can just correct the term label and equivalence axiom to match what was intended in the definition, then I am quite skeptical that it is a good idea have a term "germ cell migration" as a grouping term for "embryonic primordial germ cell migration" and any kind of "sperm migration". The first is a developmental process of primordial germ cells migrating through the embryo via a combination of hitching a ride by attaching themselves to motile cells and moving themselves via amoeboid motility while the latter is a reproductive process involving flagellated sperm migrating through the female reproductive tract. I don't think it makes sense to group the migrations of these very different ends of the germ cell developmental process as they don't share particularly much similarity in how they occur. @ukemi - Do you have thoughts about this?