Kidney - KDM Minutes

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Present: Yasmin Alam-Faruque, Emily Dimmer, David Hill, Midori Harris, Becky Foulger, Susan Tweedie, Bernard de Bono, Duncan Davidson, Randall Thomas, Adrian Woolf, Jane Lomax. Doug Howe remotely in Eugene.

David introduces GO. David's slide presentation.[]

Duncan - Nephrogenesis is not an exact synonym of kidney development

David - it can either be a new term itself or a narrow synonym of kidney development or both. So searching for nephrogenesis will bring back 'nephron development' and 'kidney development'

Kidney field development

David - we could follow the pattern of heart field development

Susan - Flies don't have kidneys, might not be wise to call malpighian tubule a synonym of kidney.

Adrian - How is GO defining a kidney

David - In the definition, urine doesn't fit for a lot of organisms

Adrian - "filter the blood and excretes the end products" - doesn't fit malpighian tubule which don't filter

Becky - need to get rid of filter part?

Randall - filtering part is not very important, kidney regulates homeostasis of the blood

Adrian - don't agree with this, in embryonic fish it is critical to get rid of water so filtration is key.

Susan - I would prefer a grouping term such as renal/excretory system

Adrian - Malpighian tubule is similar to kidney, so should be included. Is ureter part of the kidney?

David - no, it will be a separate structure

Adrian - epithelium of the ureter would be included as part of the kidney - how address this?

David - Ureter will be separate, epithelium coming from the kidney is a lineage relationship, lineage is not encoded in GO. epithelial development will be a process but not the origin of it.

Adrian - In mammalian, cells in interstitial tubes should be included

Duncan - and the vascular network

David - we have urogenital system devpt, so malpighian tubules could be part_of this? Then the two different parts of fly malpighian tubule under this

Susan - this is too broad, people will search for renal in fly terms.

Bernard - blood vessels conduct blood, endothelial cells have receptors detecting flow, growth factors then released - function is intimately linked with the maintenance of the structure, i.e. a recapitulation of the development of the structure. Where will maintenance of the structure be?

David - maintenance is not related (always) to development in GO - it is difficult to define in GO, regeneration/remodeling are also in GO and these are intimately tied to development

Becky - so we will have a renal system development?

David - yes, and we need a definition for it.

Emily - so renal will cover both kidney and malpighian tubules?

Becky - Yes, but how do the expert define the renal system?

Adrian - it will have to be broad - cells and/or organ

Randall - maintaining fluid balance is key

Bernard - what does fluid balance mean? Volume and composition?

Randall - the problem is encompassing all organisms, fish have salt excretory system

Adrian - shouldn't include filtration in the renal term

Randall - in larger mammals it is the secretion/excretion that maintains balance rather than filtration.

Adrian - water is not an excretory product

Randall - what about acid/base - does fly system contribute to this

Adrian - if we include the fluid balance and also may be important in electrolyte balance

Randall - maintains fluid balance and contributes to electrolyte and excretion of waste products and acid/base balance

Adrian - and disposal of nitrogenous waste.

David - now move kidney development term and what about urinary bladder development, is that under renal system?

Randall - some of the functions of the kidney are taken care of by the bladder

Adrian - but this is still part of renal system. Should we have in the definition, the production of urine?

Randall - fluid balance covers that as some animals don't excrete much urine

Kidney development term discussion;

David - definition of an organ is quite broad,s o that is OK in the definition

Becky - and/or excretes end products of metabolism

Randall - urologist, everything from the kidney down; nephrologist, just the kidney.

Adrian - do we want urine in the definition, is there urine in all organisms

Becky - in the definition we are only saying it produces urine, not that urinary tract is part of kidney.

David - malpighian tubules is not part of the kidney system, that is the renal system

Emily - how does def of kidney and renal differ in terms of function

Adrian - Will have to make a decision of whether to throw out other organisms

David - Susan is saying that flies don't have kidney, so we'll only include vertebrates

Emily - Taxon check for kidney development only_in vertebrates

Duncan - are we defining the kidney and then attaching the function of the structure to the definition

Adrian - I would like to see the addition of the word urine in the kidney definition

David - do we still need the 'filtration of blood'? Get rid of the and/or excretes and just have and - as we are only talking about vertebrates.

Emily - for taxon checks, is malpighian tubules just in insecta?

Susan - yes

Becky - is the kidney field the same as kidney anlage

David - pretty much

Adrian - I don't know enough about spiders, worms etc. as to whether they have kidneys or not

Randall - well we wouldn't call them kidneys, so it's OK

David - we can have a taxon check for that, it doesn't need to go into the definition

David - we can define the kidney very specifically now, and anything that doesn't fit will be put as renal system development

Kidney field discussion; David - need to make a new part_of child of 'kidney morphogenesis' called 'kidney formation' and this will be an is_a of 'anatomical structure formation involved in morphogenesis' Now make a part_of child of kidney formation called kidney field specification. Does it develop from the lateral mesoderm? IS there a specific region, if so, what is it?

Duncan - The main one would be the intermediate mesoderm, but it's not exclusive.

Midori - I can delete the intermediate and so it will be just from the mesoderm

Adrian - what about the nerve supply, this is part of the kidney field

David - in the case of heart, we do not have the nerve supply as part of heart field. Would you expect to see the nerves and mesoderm cells when you search on kidney field specification? The initial event when cells decide to give rise to kidney field

Adrian - If you want to exclude nerves, you may want to say the body of the kidney is being developed. If you say kidney, you have to include the nerves, stromal cells etc. The body is the anlagen.

David - my view is the ureteric bud invading the mesenchymal cells, these are all included in the kidney field. We can define it globally and then make more specific parts of it.

Adrian - you need kidney rudiment in there rather than the kidney

David - yes we can put in synonyms to kidney rudiment

Adrian - I don't like the word anlagen much

Becky - but it will have to be a synonym as it's used in the literature

Duncan - need to be explicit whether you mean the region or the cells

David - yes, but eventually this term will have children which are referring to the cells

Duncan - yes, that's OK

Adrian - these regions are much more well defined in the heart, regions in the mammalian kidney are not really know that well.

Yasmin - in the literature they refer to the intermediate mesoderm

Adrian - but the reviewers might be perpetuating previous authors, so it may not be the case

David - we can be quite vague about it

Duncan - if we can't say what the regions are at the moment, we can put these in when we do know.

Emily - so including kidney rudiment will stop annotation to the nervous system or vasculature?

David - yes

Becky - need term for maintenance of kidney field identity

David - need to rename 'kidney formation' to 'kidney rudiment formation'. Now onto induction of kidney rudiment. Need a term under 'kidney field specification', 'kidney induction' with a synonym 'kidney rudiment induction'. The induction occurs and then the organ is specified.

Adrian - people usually talk about induction as a later process than this

David - when we create nephrogenesis we will make an induction synonym, when they talk about induction in the literature it is not the same as in GO.

Duncan - in terms of the GO kidney induction process, very little is know about this

David - even if it's not known, it still occurs, so it's important to have it.

Duncan - but don't know about how the signalling works, whether it is close range interaction (from definition of 'X induction')

David - OK, we can get rid of the close-range part of the definition from it and the parent terms

Duncan - you are going a bit far with trying to define things that are not known

David - so you don't want the signalling part in here, if we take signalling out then we lose the induction

Duncan - why do you need the kidney induction term

Adrian - I think it is safer when you don't know the interaction of the mesenchyme, I don't like the cell-cell part. I would prefer a biological process.

Duncan - I'm happy to do without the kidney induction term

Adrian - me too

David - under kidney field specification we have request from Doug for glomerular, tubule and nephric cell specification - but these would fit better under the individual anatomical structures rather than the initial kidney field.

Doug - even though regions of the kidney field are fated to become separate anatomical structures

David - yes, we want to disconnect from the lineage of these structures. This will be covered by the cell type ontology

Duncan - this is a good idea as you don't know that these don't occur before the kidney field specification

Becky - we need the 'maintenance of kidney field identity' term under 'maintenance of organ identity' and 'kidney rudiment formation'

David - we only include the individual specific maintenance terms if they are needed by annotators, otherwise there would be lots that may not ever be used.

Yasmin - so would you want 'maintenance of pronephros identity'

David - I think it is worthwhile to add the pronephros terms because the xenopus pronephros is used as a model for kidney development and so is relevant.

Adrian - but pronephros is different in fish and mammals etc. In humans it is rudimentary but is very important in fish.

Becky - so terms underneath this would have to be defined appropriately for different species

Duncan - it might be better to separate fish and mammalian pronephros as we don't know whether in humans they are rudimentary fish structures or whether they are completely different

David - OK, so we will have to discuss whether we want them separately or not. How are we defining pronephros, is it a grouping term or does it mean completely different things? Need to think about before the end of the day.

Doug - Question is; how do we differentiate the fish, frog and vertebrate from each other. If we can clearly differentiate between them, we should make separate terms, if not, then I would prefer to keep them together.

Becky - can put taxon checks on the different child terms

Anatomical structures

David - experts can tell us what cell types, processes are contributing to each structure's development

Becky - shall we do it on a timeline, what structures develop first?

David - We want to discuss whether we want them directly under kidney or under pronephros or metanephros development?

Becky - do we want a term nephron development?

Randall - but there is also kidney nervous tissue, vasculature as well

David - yes, these will be siblings. Also need to dissociate lineage from structures, if it is a separate structure it will become a separate term

Becky - don't know whether to use nephron or tubule

Adrian - I prefer to not use tubule on it's own as it's not clear, I would use nephron and collecting duct. It's OK to use proximal/distal tubule as it's very specific. Making mesa/meta/pro-nephros terms for each organism will be hard work

David - we can have a broad term under kidney development and then make individual terms for each organism-types for mesa/meta/pro-nephros Is nephrogenesis an exact synonym of anything?

Duncan - Nephron development, not kidney development

Adrian - agreed

All agreed that, in the interests of time, all terms will be added (by Emily) to the relevant SourceForge item and the terms will be added later.

Child terms of kidney development; David - what are the substructures of kidney; collecting duct, nephron epithelium, kidney vasculature,

Duncan - would you include podocytes as nephron?

Randall - if glomerulus is part of the nephron, then podocytes should be as well

David - are developmental biologists influenced by lineage?

Duncan - very much so

Becky - in frog they talk about glomus development, is this the same as glomerulus?

Adrian - I think the glomus is wider

Becky - will make a new SF item for this

Child terms of nephron development were put into SourceForge

David - For the glomerulus terms we need to work all the way up to the renal epithelium in order to include fly

Back to Midori putting terms directly into SF

Tubule system

Discussion on the distal tubule; Distal tubule (in mammals) refers to things after the macular densa. Distal straight tubule is a misnomer, it should be thick ascending limb. Frog has a distal tubule but not a macular densa. The thin part is the intermediate tubule, and then comes the thick ascending limb, then macular densa. Macular densa development should be a new term. Connecting tubule is different structure to distal tubule. Distal convoluted tubule has it's own cell type (is_a epithelial cell).

David - we need to make cell-type differentiation terms for each of these tissues. Any synonyms for these cell-types?

Randall - yes, type I, II, etc. Will give David an article describing this (A standard nomenclature for structures of the kidney; Kriz, Bankir. The Renal Commission of the International Union of Physiological Sciences (IUPS))

Becky - Terms for S1, S2 (both proximal convoluted tubule; PT1, PT2 synonyms for Xenopus), S3 (proximal straight tubule) segments etc. in frog.

Randall - two types of nephron, short (associated with mid-cortical superficial glomeruli) and long (associated with: juxtamedullary glomeruli)

Doug - distal early and distal late tubule terms

Adrian - need to find out how these are used in the literature. Distal late may be part of the collecting duct

David - need to find out if these are going to have pro/meta/mesanephros children.

Nephron morphogenesis

Adrian - the first structure that you would recognise as a nephron epithelium is the renal vesicle. ut there are structures and events before that which you can recognise

David - what is the first structure

Adrian - mesenchyme forms into condensate, but the first nephron epithelium is the renal vesicle.

David - what about mesenchymal condensation and mesenchymal to epithelial transition as terms?

Adrian - not sure what difference is between condensation or aggregation, Jamie Davies will know.

Duncan - in this context they appear to be synonymous

David - as a sibling of mesenchymal condensation have mesenchymal to epithelial transition

Adrian - before mesenchymal condensation you need other terms, signalling events occur.

David - Is there a specific cell which is a progenitor nephron cell? We could create mesenchymal stem cell differentiation and mesenchymal stem cell maintenance.

Adrian - Six2 prevents mesenchymal cell differentiating. Is pre-tubular aggregate formation the same as mesenchymal condensation - check with Jamie Davies.

Duncan - I think they are synonymous, but check with Jamie.

David - what are the signals between the ureteric bud and mesenchyme

Adrian - at the tip of the ureteric bud there is a loop from which signalling molecules come from and act on the mesenchyme, e.g. Wnt9 and 11. BMP is made in the mesenchyme itself, so both are signalling to each other. Wnt4 is made in the condensate and is a mesenchymal factor involved in the mesenchyme to epithelial transition.

David - mesenchymal-mesenchymal signaling and mesenchymal-epithelial signaling

Adrian - Fgf2 is an anti-apoptosis factor, LIF takes the mesenchyme all the way to the nephron.

Becky - need a Loop of Henle development term

Randall - would be everything from the proximal straight tubule term until macula densa

Adrian - also need terms for comma-shaped, s-shaped structures

Adrian had to leave early at this point

Susan - need a renal tubule morphogenesis grouping term to include malpighian tubule morphogenesis

Randall - are you going to start designating regions of the kidney

David - would a developmental biologist care about the development of those regions

Duncan/Randall - yes

Randall - pre-bend segment, transition part of descending limb where the limb becomes impermeable to water