Kidney - KDM Minutes
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.. Also see: PMID 19921742
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'
- 1 Kidney field development
- 2 Kidney development terms
- 3 Kidney field terms
- 4 Anatomical structures
- 5 Child terms of kidney development
- 6 Tubule system
- 7 Nephron morphogenesis
- 8 Regions of the kidney
- 9 Collecting duct
- 10 Nephron vasculature
- 11 Stroma and interstitial cell development
- 12 Ureteric bud
- 13 SourceForge items
- 14 Other items
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 to 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 terms
David - definition of an organ is quite broad, so 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 terms
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
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
Yasmin - I have also requested terms for Glomerular mesangium development and Glomerular mesangium cell proliferation and also came across literature reference to Extraglomerular mesangial cell proliferation and Intraglomerular mesangial cell proliferation.
Adrian - yes you are right. The Intraglomerular mesangial cells derive from mesenchyme/epithelium and reside within regions of the glomerulus but the Extraglomerular mesangial cells are in the stromal region, not part of glomerulus.
Back to Midori putting terms directly into SF
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 (as we do need to xref to cell types for each of the development terms; (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.
Adrian - the first structure that you would recognise as a nephron epithelium is the renal vesicle. But there are structures and events before that which you can recognise (such as the comma shaped and s-shaped bodies).
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 ie:survival signals for mesenchyal cells and signals for stem cells to differentiate.
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. Wnt9b and 11. BMP4/7 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. Wnt7b and Brn1 involved in the regulation of collecting tubule length and diameter respectively. Wnt7b mutants - widened tubule, shortened length.
Duncan - Wnt9/9b-involved in inducing cap mesenchyme and has role in proximal tubule diameter
David - is it involved in canonical wnt receptor pathway?
Duncan - need to check.
David - mesenchymal-mesenchymal signaling and mesenchymal-epithelial signaling
Adrian - Wnt7b is interesting as it signals via the interstitium mesenchyme to the collecting duct. 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 Juxtaglomerular cells are next to the macular densa. Juxtaglomerular apparatus contains part of nephron
Regions of the kidney
Randall - Inner/outer stripe, inner/outer medulla, pyramids, cortex, vasculature
Randall - connecting tubule (syn: connecting duct), outer/inner medullary, cortical collecting duct,
Duncan - controlling the diameter of collecting duct are Wnt7b (also regulates collecting duct length - David doesn't like regulation of lengths as it is a biological quality) and BRN1. Wnt9b induces mesenchyme and has a role in proximal tubule and collecting duct (possibly) diameter. Wnt7b expressed in collecting duct but it's signaling is via the interstitial mesenchyme.
Randall - (see previous article cited): Types of cells in these tissues are:
*proximal (thick) tubule (S1, S2, S3 cells),
*descending thin limb (type 1 (only in short descending thin limbs), type 2 (in long descending thin limb), type 3 (in long descending thin limb)),
*ascending thin limbs (type 4 cell, atl cells),
*thick ascending limb (thick ascending limb (tal) cells - long nephrons with differential expression pattern),
*distal convoluted tubule (dct cells), early distal convoluted tubule (dct cells)-immediately after macula densa, insensitive to water permeability and sensitive to vasopressin after that as epithelium becomes permeable again, late distal convoluted tubule (dct cells and alpha and beta intercalated cells - difference in transporters expressed on cells),
*connecting tubule (cnt cell and intercalated cells (same as previous intercalated cells)),
*collecting duct (principal cells and intercalated cells at beginning, but further into the medullary duct there is only principal cells). Short nephron (Def: associated with mid-cortical superficial glomeruli. Have no short ascending limb therefore the s d limb is situated in the outer medulla have different transporters/ion channels. (Authors: Pannabecker, Dantzler, Christensen(mouse))
Epithelium is sensitive to vasopressin. Contains vasopressin receptors. In descending limb-ascending limb the cells are impermeable to water until they are at prebend segment.
Susan - In flies there are the stelate cells - will have to check what these cells are in the fly.
David - if they are performing the same function, then they are classed as the same cells
Duncan - does Drosophila malpighian tubule have a vasculature?
David - no they just have an open system
Randall - vascular bundle, structure or not? A group of vessels in the inner stripe of the outer medullary. (has adult renal physiome ontology terms in his database)
David - Renal artery - is it's development considered part of kidney development as it extends beyond the kidney?
Duncan - yes. There is an intrarenal segment of the renal artery.
Stroma and interstitial cell development
Duncan/Randall - should be a direct child of kidney development. Arguments about whether stroma and interstitial are the same thing, ask Jamie and others (Kathy Mendelsen?-expert Paris group - Randy to send details).
Duncan - there are regions from the nephrogenic mesenchyme (directly under kidney development) that become stroma. Interstitial cells secrete extracellular matrix. Cells at periphery of mesenchyme some become stroma, some become nephron.
David - For specific areas of mesenchyme: have two terms under kidney development; kidney epithelium development, kidney mesenchyme development. Child of kidney mesenchyme is metanephric mesenchyme development and this has a child nephrogenic mesenchyme development (check this with Jamie, also check difference between metanephric and nephrogenic mesenchyme)
Duncan - Branching, Tip maturation, Differentiation of ureteric tip cells (which differentiate prior to branching)
Randall - there is also the renal capsule which holds the whole kidney structure together. Papilla have peristaltic movement - papillary peristalsis.
Yasmin - has needed to request a term for ureteric peristalsis and renal/ureteric smooth muscle cell differentiation.
Duncan - also the calyx
There was discussion on the development of a process rather than development of an anatomical structure e.g. development of circulation; development of muscle contraction. Duncan, David and Jane to generate a short feasibility study. Could work well for systems biology.
Review of all the current SF items relating to kidney development.
Duncan - Podocyte is a type of visceral epithelial cell, possibly also generated from an endothelial cell. There is also the glomerular capillary tuft. Podocyte is atype of glomerular tuft but not necessarily synonymous with that as it can be also generated from endothelial cells.
Susan - drosphila have podocyte cells. Need to see if they are distinguished within the kidney.
Rachael - GO already has 'ureteric bud elongation', is this different to 'ureteric bud invasion'? - yes - so should create a new term
Becky - will create new SF request for glomus development (Xenopus)
David - Precursor epithelial cells; progenitor cells; podocytes=visceral epithlial cells. Need to make a new term for 'ureteric bud invasion' as distinct from 'ureteric bud elongation' as signalling is involved in the invasion whereas elongation is just the extension of the bud. BMP4 signalling involved in urinary tract segmentation - new term; 'cell-cell signalling involved in pattern formation' under 'nephron patter formation'. Is this patterning or segmentation? (Yasmin will need to recheck PMID 17442697 for region specification but title refers to segmentation).
- Nephron morphogenesis; --<nephron pattern formation; --<cell-cell signalling involved in nephron pattern formation; --<Regulation of nephrogenic mesenchyme cell proliferation. (Note to Yasmin: 'differentiation' terms always involve a cell type; --<mesenchymal cell proliferation
Head kidney development - is_a type of pronephros? - Duncan agrees
Kidney epithelium differentiation - will actually be 'Kidney epithelial cell differentiation' which will be a child of 'kidney epithelium development'
Midori will put into the scratch directory, make correct parentages and definitions together with David and then send out a diff file to everyone for comments.
We have created 76 new terms today!!
- also discussed renal pattern specification; --<kidney pattern specification; --<proximal-distal pattern specification (pattern formation); --<anterior-posterior pattern specification
- need to create pronephros, mesonephros child terms required for these anatomical developmental terms.
- did not cover fully: kidney nervous system
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