additional germ layer specification terms

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Don't know if this topic has come up before, but I would like to suggest the addition of two new terms under cell fate specification GO:0001708. Could we add mesendoderm specification and mesectoderm specification as additional child terms of cell fate specification? The definitions could mirror those already in existence for ectoderm, endoderm, and mesoderm specification, but indicate that these are the processes that specify the fate of tissue that gives rise to both mesoderm and endoderm or mesoderm and ectoderm.

Thanks, Kimberly Van Auken WormBase-Caltech.

Reported by: vanaukenk

Original Ticket: "geneontology/ontology-requests/1374":https://sourceforge.net/p/geneontology/ontology-requests/1374

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I thought about this when we originally specified the three germ layers. The difficulty I had with these terms is that I couldn't find a way to fit them into the graph without creating a true path violation with repect to endo,meso and ectoderm specification. I thought we could get around this in 2 ways. 1) Annotate the gene to both ectoderm and mesoderm specification. 2) Create a term for the specification of the tissue, then make two parts of that, the ectodermal component and the mesodermal component for example each of these would then be a type of their respective parents.

I think #2 works best and it is already reflected in the mouse anatomical dictionary. For example the optic eminence is broken down into its ectodermal component and its mesodermal component.

Once we have slots, each of these will become a type of the generic parent.

Original comment by: ukemi

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Hi David,

Thanks for your comments about mesendoderm and mesectoderm specification. I have been looking over the ontologies, the true path rule documentation, and thinking more about what process I'm really trying to annotate with these terms. In the course of doing this, I've found a helpful review article regarding mesendoderm development at http://www.cell.com/content/article/fulltext?uid=PIIS0092867401003075.

In the early C. elegans embryo, a single blastomere, EMS, gives rise to all of the endoderm and some of the mesoderm. There are several transcription factors, namely SKN-1, MED-1, and MED-2, that specify EMS/mesendodermal development, and I would like to assign a GO term to these gene products to describe their role in this process. Would it be possible to add mesectodermal and mesendodermal development to the ontology in the following way without violating a true path rule? I could then annotate these gene products to the last term, mesendoderm development.

biological_process I development I morphogenesis I organogenesis P histogenesis [GO:0009888] I ectoderm development I endoderm development I mesoderm development I mesectoderm development I mesendoderm development

Also, could you explain in more detail how a term like "mesendoderm cell fate specification" would violate the true path rule? I want to make sure I understand where the difficulties lie with adding this kind of term to the ontology.

Thanks again, Kimberly

Original comment by: vanaukenk

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Hi Kimberly,

The structure that is below doesn't violate the true path, but I think it is incomplete. If we introduce the term mesendoderm development, then I think it needs to relate to both endoderm development and mesoderm development in some way. That is when The true path violations rear their heads. If we make mesendoderm development a parent of mesoderm development and endoderm development then all mesoderm and endoderm must go through a mesendoderm state. I'm not sure this is always correct, although it could be argued if you trace lineage back far enough. Conversely, if we make mesendoderm development a child of both endoderm development and mesoderm development then mesendoderm development has to always happen as well. But, I can see why you want this term!

How about this:

mesoderm formation -%mesoderm formation via mesendoderm --<mesendoderm cell fate commitment --<mesendoderm development into mesoderm endoderm formation -%endoderm formation via mesendoderm --<mesendoderm cell fate commitment --<mesendoderm development into endoderm

then cell differentiation -%mesendoderm cell differentiation --<mesendoderm cell fate commitment --<mesendoderm cell developement ---%mesendoderm development into endoderm ---%mesendoderm development into mesoderm

also note that the graphs below ecto, meso and endoderm formation are incomplete. They should have ecto, meso and endoderm cell differentiation as part of children with the correct structure following generic cell differentiation.

Please check the logic and let me know if you think this works.

David

Original comment by: ukemi

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Hi David,

(Keep in mind that plants don't have any of these germ layers but here's my opinion anyway.)

If we go with the structure you propose below (taking one layer as an example):

mesoderm formation -%mesoderm formation via mesendoderm --<mesendoderm cell fate commitment --<mesendoderm development into mesoderm

Is there another way of forming the mesoderm without going through a mesendoderm? From Becky's emails, it sounds like there is. If so, where would 'mesoderm cell fate specification' fall in the graph above? Would it have a relationship to 'mesendoderm cell fate specification' or not?

Tanya

Original comment by: tberardini

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Hi Tanya,

It would not be a part of mesendoderm cell fate specification, because is is not a part of it, happens afterwards. It would fall under:

mesoderm formation GO:0001707 -<mesoderm migration GO:0007509 -<mesoderm cell differentiation GO:NEW1 --%mesendoderm development into mesoderm GO:NEW2 --<mesoderm cell fate commitment GO:0001710 ---<mesoderm cell fate specification GO:0007501 ---<mesoderm cell fate determiantion GO:0007500 -%mesoderm formation via mesendoderm GO:NEW3 --<mesendoderm cell fate commitment GO:NEW4 --<mesendoderm development into mesoderm GO:NEW2

Original comment by: ukemi

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Got it.

Thanks,

Tanya

Original comment by: tberardini

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I agree that we should accommodate the separate mesendodermal and non-mesendodermal origins of mesoderm. Im not clear on how that works in the following graph snagged from Davids message:

mesoderm formation GO:0001707 -<mesoderm migration GO:0007509 -<mesoderm cell differentiation GO:NEW1 --%mesendoderm development into mesoderm GO:NEW2 --<mesoderm cell fate commitment GO:0001710 ---<mesoderm cell fate specification GO:0007501 ---<mesoderm cell fate determiantion GO:0007500 -%mesoderm formation via mesendoderm GO:NEW3 --<mesendoderm cell fate commitment GO:NEW4 --<mesendoderm development into mesoderm GO:NEW2

Would the formation of NON mesendodermally-derived mesoderm be annotated to GO:NEW1 (or GO:0001707?) and the formation of mesendodermally-derived mesoderm be annotated to GO:NEW2?

Original comment by: doughowe

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Thanks for the review Kimberly! At the bottom of the review (An Ancient pathway?) it states:

Since Drosophila is not thought to generate a mesendodermal precursor to endoderm and heart or blood mesoderm....

So I like the tree you suggest for mesendoderm terms David- Drosophila not having a mesendoderm doesn't create a problem.

Are you suggesting the same layout for mesectoderm? If so, I am a little worried that using 'mesectoderm cell fate commitment' will create a TPV for us. The ventral midline is derived from mesectodermal cells in Drosophila. The gene 'sim' is responsible for mesectoderm cell fate commitment. But it is involved in ventral midline formation, not 'mesoderm formation via mesendoderm'.

Maybe the best way to do this is to create a sensu Protostomia or sensu Insecta term for mesectoderm cell fate commitment, that is not under mesdoerm formation via mesendoderm, or mesoderm formation?

see PMID: 10869780 for the Drosophila perspective on mesectoderm.

Thanks, Becky

Original comment by: beckyfoulger

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Q. Would the formation of NON mesendodermally-derived mesoderm be annotated to GO:NEW1 (or GO:0001707?)

A. It depends on the process. If it is the differentiation of "blastomeres" if you will into mesoderm then GO:New1. If it is another process, like migration or something else that happens it would go with 1701 or a term to be added later. In this case GO:NEW2 is a subclass of 1701. All other type can be annotated to 1701. If in the future we can define other subtypes, then we could make new terms like mesoderm formation via a blastomere, but I don't think that is really necessary unless we want to get that specifc.There was one point in time where I thought if a process had an is_a child, then it should have at least two is_a children, one for the subclass and one for everything other than the subclass. I think this is logically true, but it doesn't need to be instantiated so explicitly.

Q. formation of mesendodermally-derived mesoderm be annotated to GO:NEW2?

A. Yes.

David

Original comment by: ukemi

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Kimberly,

I bet you didn't think this would generate so much discussion. Mesectoderm is trickier because it has more than one meaning. I think that this should be handled under the cell differentiation since the distinction is in cell types! So if you go way down this record, you see that I've also created:

Original comment by: ukemi

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Kimberly,

I bet you didn't think this would generate so much discussion. Mesectoderm is trickier because it has more than one meaning. I think that this should be handled under the cell differentiation since the distinction is in cell types! So if you go way down this record, you see that I've also created:

-%mesendoderm cell differentiation --<mesendoderm cell fate commitment --<mesendoderm cell developement ---%mesendoderm development into endoderm ---%mesendoderm development into mesoderm -%mesectoderm cell differentiation --<mesectoderm cell fate commitment ---<mesectoderm cell fate determination ---<mesectoderm cell fate specification --<mesectoderm cell developement --%mesectoderm cell differentiation (sensu vertebrate) --%mesectoderm cell differentiation (sensu protostoma) --%mesectoderm cell differentiation (sensu nematoda)

All of these would have the appropriate children. The reason why I favor the split at this level is because it separatesw the differences of the actual cell types in the differentiation stage, where the distinction is made. We could then ask the folks from the cell type ontology to create three types of mesectoderm cells. When we deconstruct this we would just choose th right cell typs and we'd be all set.

David

Original comment by: ukemi

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Please note that whenever I propose a cell differentiation term, it should always have the structure:

differentiation -<commitment --<specification --<determination -<development or maturation

under it even if I don't type them all out!

David

Original comment by: ukemi

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This works for me!

Thanks, Becky

Original comment by: beckyfoulger

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I think this proposed sturcture works.

Original comment by: doughowe

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I think these additions to the ontology will work well for accomodating the developmental processes involving mesendoderm and mesectoderm. Thanks to everyone for their very helpful input.

Kimberly

Original comment by: vanaukenk

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Original comment by: jenclark

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Original comment by: jenclark

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Hi,

I've just been reading through this sourceforge item and I noticed a comment made early on in the discussion that could perhaps be re-thought in the light of Chris Mungall's explanation of the different kinds of part_of.

The comment was:

David Hill: 'The structure that is below doesn't violate the true path, but I think it is incomplete. If we introduce the term mesendoderm development, then I think it needs to relate to both endoderm development and mesoderm development in some way. That is when The true path violations rear their heads. If we make mesendoderm development a parent of mesoderm development and endoderm development then all mesoderm and endoderm must go through a mesendoderm state. I'm not sure this is always correct, although it could be argued if you trace lineage back far enough. Conversely, if we make mesendoderm development a child of both endoderm development and mesoderm development then mesendoderm development has to always happen as well. But, I can see why you want this term!'

I think that maybe the logic of this is assuming that the part_of relationship is necessarily_has_part rather than necessarily_is_part. If you redo that argument with necessarily_is_part then you get:

If we make mesendoderm development a parent of mesoderm development and endoderm development then mesoderm and endoderm development may not occur outside of mesendoderm development. According to the review quoted in this sourceforge item, they do, so that wont work. Conversely, if we make mesendoderm development a child of both endoderm development and mesoderm development then mesendoderm development cannot occur without being part of both mesoderm development and endoderm development. I'm not sure enough of the biology to know if this is ok.

I wrote to David Hill to check if I was understanding his comment correctly and he said this:

David: 'As GO stands now, if you are a part-of something, you don't always have to occur. So, it seems that mesendoderm development is both a part-of endoderm and a part-of mesoderm development, because it is sometimes a part of both.'

So I wondered, in the light of this change, if that means that I could make mesendoderm development as a new term that is a part-of endoderm development and a part-of mesoderm development, so as to answer the problem in that sourceforge item, or if there is a more complicated issue there?

Thanks,

Jen

Original comment by: jenclark

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Hi Jen,

I have a question about the part-of logical relationships being used in GO. If I understand David's comment correctly, he is saying that mesendoderm development is sometimes a part of endoderm development and sometimes a part of mesoderm development, but that endoderm and mesoderm development does not always proceed via formation of mesendoderm. This fits with what I think I understand about development :).

David: 'As GO stands now, if you are a part-of something, you don't always have to occur. So, it seems that mesendoderm development is both a part-of endoderm and a part-of mesoderm development, because it is sometimes a part of both.'

So, my question is: does GO ever use the sometimes_part_of relationship, or are the necessarily_has_part and necessarily_is_part relationships the only ones used in GO?

Thanks, Kimberly

Original comment by: vanaukenk

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Hi Kimberly,

Jane has written some new documentation to help explain the use of part_of in the gene ontology: http://www.geneontology.org/GO.usage.html\#partof Hopefully this should answer your question but if you'd like to know more then please do ask. We can add more to the documentation if there are more unanswered questions there.

My questions are more to do with the biology since, as a plant scientist, I am not familiar with mesendoderm biology (I have been reading a text book and the review quoted below). According to the part_of rules in GO mesendoderm development can be part_of mesoderm development if the following criteria hold:

1) mesendoderm development is sometimes part of mesoderm development.

2) sometimes mesoderm development occurs without having mesendoderm development as part of the process.

3) Mesendoderm development never occurs except as part of mesoderm development.

Likewise for endoderm development. From your knowledge of the biology would you say that these hold?

Thanks,

Jen

Original comment by: jenclark

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Hi Jen,

From my knowledge of developmental biology, I would say that the following three criteria do hold true for mesendoderm development. If these criteria are untrue for other organisms of whose development I am not aware, hopefully someone else with more expertise will chime in here!

1) mesendoderm development is sometimes part of mesoderm development.

2) sometimes mesoderm development occurs without having mesendoderm development as part of the process.

3) Mesendoderm development never occurs except as part of mesoderm development.

And thanks for the link to the part_of documentation. I'll read it over and ask if I have any more questions.

Cheers, Kimberly

Original comment by: vanaukenk

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Hi,

Shall I plan to add the following terms on Monday 10th May then? That will give people plenty of time to comment.

%histogenesis -%mesoderm development --<mesendoderm development -%endoderm development --<mesendoderm development

%histogenesis -%mesoderm development --<mesectoderm development -%ectoderm development --<mesectoderm development

mesectoderm development, GO:new def: Biological processes specifically aimed at the progression of the mesectoderm over time, from its initial formation to a mature structure. In animal embryos, mesectoderm development processes specify the fate of tissue that gives rise to both mesoderm and ectoderm tissues.

mesendoderm development, GO:new def: Biological processes specifically aimed at the progression of the mesendoderm over time, from its initial formation to a mature structure. In animal embryos, mesendoderm development processes specify the fate of tissue that gives rise to both mesoderm and endoderm tissues.

Thanks,

Jen

Original comment by: jenclark

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Unless I am mistaken, the query that started this SF item was interested in getting terms under cell fate specification. The terms we have arrived at describe tissue development, not cell specification. I think the tissue terms Jen just proposed adding would be good, but do we still need terms under cell fate specification?

-Doug

Original comment by: doughowe

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Doug et al,

Yes, I think we should add the cellular terms appropriately. If you go back to the original exchanges in this discussion they were to be added under the tissue terms.

David

David

Original comment by: ukemi

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David et al,

Yes, this was my understanding, as well. We would add both the cellular terms and the tissue terms to capture the whole process of mesendoderm or mesectoderm development.

--Kimberly

Original comment by: vanaukenk

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Ooops sorry. You're right. I'll go back and try that again.

Jen

Original comment by: jenclark

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Hi,

Kimberly mentioned in the second comment below that development terms might be sufficient to solve the annotation problem she has. Do you think it would be good if I add the development terms to help with the annotation problem and we can get on and think about cell fate specification problems next? I've been trying to think of how to deal with the cell fate specification terms and it seems to me that they might take some work to sort out and it might help if we can at least get the development terms in place as a first step.

Jen

Original comment by: jenclark

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I think this would be o.k. with me if we can't resolve the cell differentiation issues.

Original comment by: ukemi

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Hi,

I have added these new terms so annotations can be made while we work out what to do about the specification terms.

%histogenesis -%mesoderm development --<mesendoderm development ; GO:0048382 (new) -%endoderm development --<mesendoderm development

%histogenesis -%mesoderm development --<mesectoderm development ; GO:0048383 (new) -%ectoderm development --<mesectoderm development

mesectoderm development, GO:new def: Biological processes specifically aimed at the progression of the mesectoderm over time, from its initial formation to a mature structure. In animal embryos, mesectoderm development processes give rise to both mesoderm and ectoderm tissues.

mesendoderm development, GO:new def: Biological processes specifically aimed at the progression of the mesendoderm over time, from its initial formation to a mature structure. In animal embryos, mesendoderm development processes give rise to both mesoderm and endoderm tissues.

Jen

Original comment by: jenclark

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Original comment by: jenclark

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Original comment by: jenclark

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Hi,

This item has been open for a long time. Please comment to let us know whether you would like it to remain assigned to you, or would prefer it to be reassigned. (You don't necessarily have to work on it immediately if you keep it; we just need to know whether it's still on your list.)

Thanks, Midori & David Ontology development group managers

Original comment by: mah11

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Hi,

I'll try to spend some time on this item to see what outstanding issues we might be able to resolve. This likely won't be a high priority item for me, but I will try to re-visit the topic within the next few weeks to see what can be done.

--Kimberly

Original comment by: vanaukenk

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Hi Kimberly,

Shall we just close this and we can open a new item if other terms are ever needed? I'm trying to close of stagnant old items so that we can figure out which ones actually do need our attention.

Thanks,

Jen

Original comment by: jenclark

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Yes, this sounds reasonable.

Thanks, Jen.

--Kimberly

Original comment by: vanaukenk

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• status: open --> closed-accepted

Original comment by: jenclark