Kidney Development

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Kidney Development Ontology Content Meeting January 2010

Agenda for Kidney Development Ontology Content Meeting

Meeting at HGU 22nd June 2009

Participants: Duncan Davidson, Jamie Davies, Simon Harding, Jane Armstrong (Edinburgh GUDMAP team)
Yasmin Alam-Faruque, Emily Dimmer (EBI GOA)

Minutes available (requires access to EBI GOA Confluence)

Suggested GO Terms for Nephrogenesis

List from the White Board – All are ‘Biological Process’

  • Stem cell maintenance,
  • Elective cell death,
  • Cell division,
  • Leaving the stem cell compartment,
  • Mesenchymal cell condensation,
  • Chemotaxis in mesenchymal cells,
  • Sensing a quorum of cells / control of the number of cells in a cell group,
  • Mesenchyme to epithelium transition,
  • Formation of tight junctions,
  • Formation of zona adherens,
  • Formation of basement membrane,
  • Epithelial cell polarization (apical/basal polarization),
  • Epithelial patterning,
  • Differentiation of cell types,
  • Morphogenesis of epithelial tubules,
  • Oriented mitosis,
  • Cell shape change,
  • Programmed cell death / apoptosis,
  • Formation of renal vesicle,
  • Formation of comma-shaped body,
  • Formation of s-shaped body,
  • Formation of glomerulus,
  • Formation of mesangium,
  • Formation of … each anatomical structure,
  • Signalling to blood vessel-forming cells,
  • Connection of nephron tublule to collecting duct,
  • Migration of kidney (from pelvis to upper lumbar/ lower thoracic region).

Working list

adapted from the white board list by looking at existing terms in GO using QuickGO (working draft)

Please note that there are many more cell types and anatomical structures to add here, see below under differentiation of …. (cell type) and formation of.. (structure). This is something we should perhaps do soon, but probably working with experts in adult nephron anatomy at least some of whom we already collaborate with and may be able to help, for example Prof. Brigitte Kaissling in Zurich. Of course this is all quite coarse granularity so I expect we will be adding terms for some time.

My aim was simply to get the list to the state where existing GO terms are used where possible and to suggest terms where we think there may be none existing. I think this is worth the small effort since we can probably best judge whether an existing term suits. I don’t plan to go through GO to look for more terms at the moment, so am just using the terms we came up with in the white board list. I have added a few definitions just to see how easy it would be to adapt existing definitions to the case of the nephron.

Now that we have done this, I assume it’s over to Yasmin and colleagues to sort out our suggestions in relation to the GO DAG and GO conventions.

List – DD, JD Thursday, July 2, 2009

Existing GO terms

  • GO:0035019 somatic stem cell maintenance,
  • GO:0048864 stem cell development,
  • GO:0048863 stem cell differentiation,
  • GO:0048103 somatic stem cell division.
  • GO:0060231 mesenchymal to epithelial transition,
  • GO:0010717 regulation of epithelial to mesenchymal transition,
  • GO:0045198 establishment of epithelial cell apical/basal polarity,
  • GO:0008360 regulation of cell shape,
  • GO:0012501 programmed cell death,

Suggested new GO terms

  1. Nephrogenic stem cell differentiation [Defn: The process whereby a relatively unspecialized cell acquires specialized features of a nephrogenic stem cell. A stem cell is a cell that retains the ability to divide and proliferate throughout life to provide progenitor cells that can differentiate into specialized cells.]
  2. Commitment of multipotent stem cells to the nephrogenic lineage [Defn: The initial commitment of cells whereby the developmental fate of a cell becomes restricted such that it will develop into some type of cell in the nephron.]
  3. Mesenchymal cell condensation involved in nephron development [Defn: the cell adhesion process by which nephron precursor mesenchyme cells adhere to one another to form the pretubular aggregate in the initial stages of nephron development.]
  4. chemoattraction of in mesenchymal cells involved in nephron development [Defn: I am not sure if there is sufficient evidence for the involvement of chenotaxis in the formation of the pretubular aggregate - Jamie? If not, I presume it should be deleted for the time being?]
  5. Sensing a quorum of cells / control of the number of cells in a cell group
  6. Mesenchyme to epithelim transition in the metanephric kidney,
  7. Formation of tight junctions,
  8. Formation of adherens junctions,
  9. Formation of basement membrane,
  10. Epithelial patterning of the nephron epithelium {Syn: segmentation of the nephron epithelium},
  11. new children of GO:0002070 epithelial cell maturation,
    1. Podocyte differentiation,
    2. Proximal tubule cell differentiation,
    3. Loop of Henle cell differentiation,
    4. Distal tubule cell differentiation,
    5. Connecting tubule cell differentiation,
    6. ..........Differentiation of all other nephron cell types.
  12. Formation of renal vesicle,
  13. Formation of comma-shaped body,
  14. Formation of s-shaped body,
  15. Formation of glomerulus,
  16. Formation of mesangium,
  17. ..........Formation of each anatomical structure.
  18. Morphogenesis of epithelial tubules (I think this is not GO:0001838 embryonic epithelial tube formation or GO:0060562 epithelial tube morphogenesis because it is not the formation of the tube but the morphogenesis of its form from a spherical vesicle to a comma shape and thence to an S shape). What is the difference between GO:0001838 embryonic epithelial tube formation and GO:0060562 epithelial tube morphogenesis? The definitions are very similar. Pretty similar also to GO:0035239 Tube morphogenesis. We need something that does not denote the generation and organization of tubes, but their subsequent changes in shape. One possibility would be 'comma-shaped body morphogenesis, but it would be good to have a more general ancestor term so that one could link basic processes that occur in the morphogenesis of different forms of epithelial tube.
  19. Regulation of epithelial tubule diameter (is_a GO:0035296 regulation of tube diameter)
  20. Oriented mitosis (could not find such a term in GO - not GO:0008356 asymmetric cell division)
  21. Cell morphogenesis
  22. Signalling to blood vessel-forming cells (need to ask Jamie about this - is it GO:0060684 epithelial-mesenchymal cell signaling?)
  23. Connection of nephron tubule to collecting duct

GO curator comments


New term items 7-9: I've added two new terms; we already had adherens junction assembly

  • 7. tight junction assembly GO:0070830 (synonym: tight junction formation) (NEW)
  • 8. adherens junction assembly GO:0034333 (synonym: adherens junction formation)
  • 9. basement membrane assembly GO:0070831 (synonym: basement membrane formation) (NEW)

(midori 2009-07-23)


As before, numbers refer to the numbered list of suggested new GO terms above.

  • 1. Is a 'nephrogenic stem cell' the same as 'metanephric mesenchyme stem cell' in the cell type ontology (CL:0000324)? If so, I'll include a synonym in GO and request a synonym in CL; if they're different, I'll request a new CL term. Either way, it's so we can construct a GO-CL cross-product for the GO term.
  • 2. GO would word the term name as 'nephrogenic stem cell fate commitment'; we can include the suggested phrase as a synonym if that's what kidney experts are likely to search for. Following the standard structure we've implemented for cell differentiation terms (documentation), this term would have a part_of link to new term #1.
  • 5. The existing term 'homeostasis of number of cells within a tissue' (GO:0048873) might work here, or, if you want something more specific, we could add a new child term. I would try to avoid 'sensing a quorum of cells' because we have a term named 'quorum sensing' that is defined so as to be specific for single-celled organisms.
  • 11. It would be very good if we could suggest new terms to add to the CL ontology for these nephron cell types. And eventually GO curators will need a list of the other nephron cell types for which you need differentiation terms. We'll put the new terms under 'epithelial cell differentiation' (GO:0030855), and if you specifically need maturation terms, we'll add those as well.
    • (note to self - podocyte is in CL but not defined; CL:0000653)
  • 20. I suggest using 'establishment of mitotic spindle orientation' (GO:0000132) for this. The rationale is that the distinguishing feature of "oriented mitosis" is that the spindle is positioned such that division takes place in a specific plane. Everything else is just the usual chromosome condensation, spindle attachment, alignment at metaphase plate, chromosome movement, etc. that are common to all instances of mitosis. We could add a child term if there are gene products that specifically act in spindle orientation during kidney development but not in other places or at other times (e.g. 'establishment of mitotic spindle orientation involved in kidney development').



  • wrt point #1.

Response from Duncan Davidson (GUDMAP): 1. I'd suggest that the most helpful thing here would be to define nephrogenic mesenchyme and metanephric mesenchyme. 'Nephrogenic stem cell fate commitment' could perhaps mean the commitment of a cell to the fate of being a nephrogenic stem cell, or the commitment of one of the daughters of division in a nephrogenic stem cell to being part of a nephron. Am I right that the term denotes the former?

Response from Jamie Davies (GUDMAP): 1. Yes. I have always used the term 'metanephrogenic mesenchyme' (and several others do too) in order to combine these terms and also be clear that I am not talking about the mesenchyme of an adult metanephros but rather the stem compartment of the earlier kidney. This term is not in the GUDMAP ontology, though, so you won't want to use it. In either case, I don't think that anyone has defined a stem cell definitely capable of self-renewal but giving rise to nephron but to nothing else (ie not to stroma). Indeed, the ability to even adult nephron cells to undergo EMT and give rise to stroma would suggest that a stem cell committed to forming only nephron and nothing else cannot exist.

  • wrt point #2.

Response from Jamie Davies(GUDMAP): 2. I think for all commitments, you need to state 'commitment to...' (otherwise the ambiguity mentioned in Duncan's comments will always be there).

  • wrt points #5, #11, #20.

Response from Jamie Davies(GUDMAP): Agreed.

(Yasmin 02/09/09)


Response to 'nephrogenic stem cell fate commitment' question raised for point #1:

In GO, all cell fate commitment terms are defined as committing the cell to the fate of being the named cell type; in other words, "X cell fate commitment" means fated to become a cell of "X" type. For "stem cell fate commitment" (GO:0048865), the GO term specifically refers to commitment to become a stem cell, and does not extend to any downstream fates resulting from further differentiation of the stem cell. The same applies to any is_a children of GO:0048865, so 'nephrogenic stem cell fate commitment' does refer to the commitment of a cell to the fate of being a nephrogenic stem cell. Because of the consistency that GO has imposed in this area, we will continue to use "X cell fate commitment" term names, but we can add comments to dispel any confusion or ambiguity that might otherwise befall annotators or other users.


SourceForge Links

SourceForge items relevant to kidney development

Ontology Editing

Ontology editing notes on Kidney Development Meeting page

For discussions on kidney physiology, see: [[1]]