Development of ureteric collection system (WP5053)

Homo sapiens

This pathway describes the gene signalling pathway active in the development of the ureteric collection system in human kidney development. Mutations in essential genes within this pathway can lead to development of CAKUT (congenital anomalies of the kidney and urinary tract).

Authors

Friederike Ehrhart

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Homo sapiens

Communities

Rare Diseases

Annotations

Pathway Ontology

signaling pathway

Disease Ontology

kidney disease CAKUT

Participants

Label Type Compact URI Comment
Cyclopamine Metabolite chebi:4021
CTNNB1 GeneProduct ensembl:ENSG00000168036
ILK GeneProduct ensembl:ENSG00000166333
GATA3 GeneProduct ensembl:ENSG00000107485
ETV4 GeneProduct ensembl:ENSG00000175832
FREM2 GeneProduct ensembl:ENSG00000150893
GRIP1 GeneProduct ensembl:ENSG00000155974
VANGL2 GeneProduct ensembl:ENSG00000162738
CELSR1 GeneProduct ensembl:ENSG00000075275
ROBO1 GeneProduct ensembl:ENSG00000169855
FAT4 GeneProduct ensembl:ENSG00000196159
LHX1 GeneProduct ensembl:ENSG00000273706
ITGB1 GeneProduct ensembl:ENSG00000150093
FGFR2 GeneProduct ensembl:ENSG00000066468
ROBO2 GeneProduct ensembl:ENSG00000185008
GPC3 GeneProduct ensembl:ENSG00000147257
FOXC1 GeneProduct ensembl:ENSG00000054598
HOXD11 GeneProduct ensembl:ENSG00000128713
BMP5 GeneProduct ensembl:ENSG00000112175 found only in mouse so far
CCND1 GeneProduct ensembl:ENSG00000110092 CyclinD1
WT1 GeneProduct ensembl:ENSG00000184937
RARA GeneProduct ensembl:ENSG00000131759
SHH GeneProduct ensembl:ENSG00000164690
RET GeneProduct ensembl:ENSG00000165731
BMP4 GeneProduct ensembl:ENSG00000125378
GREB1L GeneProduct ensembl:ENSG00000141449
RARG GeneProduct ensembl:ENSG00000172819
PBX1 GeneProduct ensembl:ENSG00000185630
GDF11 GeneProduct ensembl:ENSG00000135414
FST GeneProduct ensembl:ENSG00000134363 found only in mouse so far
CTDNEP1 GeneProduct ensembl:ENSG00000175826 found only in mouse so far
MYCN GeneProduct ensembl:ENSG00000134323 N-MYC
TGFB2 GeneProduct ensembl:ENSG00000092969
BMPER GeneProduct ensembl:ENSG00000164619
CRIM1 GeneProduct ensembl:ENSG00000150938 found only in mouse so far
ANOS1 GeneProduct ensembl:ENSG00000011201 also known as KAL-1, KAL1
SIX1 GeneProduct ensembl:ENSG00000126778
ITGA8 GeneProduct ensembl:ENSG00000077943
SALL1 GeneProduct ensembl:ENSG00000103449
FRAS1 GeneProduct ensembl:ENSG00000138759
SPRY1 GeneProduct ensembl:ENSG00000164056
GREM1 GeneProduct ensembl:ENSG00000276886
BMPR1A GeneProduct ensembl:ENSG00000107779
SMAD1 GeneProduct ensembl:ENSG00000170365
BMP7 GeneProduct ensembl:ENSG00000101144 found only in mouse so far
EYA1 GeneProduct ensembl:ENSG00000104313
RARB GeneProduct ensembl:ENSG00000077092
HOXA11 GeneProduct ensembl:ENSG00000005073
SLIT2 GeneProduct ensembl:ENSG00000145147
WNT11 GeneProduct ensembl:ENSG00000085741
GFRA1 GeneProduct ensembl:ENSG00000151892
PAX2 GeneProduct ensembl:ENSG00000075891
GDNF GeneProduct ensembl:ENSG00000168621
BMP2 GeneProduct ensembl:ENSG00000125845 found only in mouse so far
GLI1 GeneProduct ensembl:ENSG00000111087
SMO GeneProduct ensembl:ENSG00000128602
BMPR2 GeneProduct ensembl:ENSG00000204217
GLI3 GeneProduct ensembl:ENSG00000106571
FRAS1 GeneProduct ensembl:ENSG00000138759
FREM1 GeneProduct ensembl:ENSG00000164946
SIX2 GeneProduct ensembl:ENSG00000170577
GLI2 GeneProduct ensembl:ENSG00000074047
TCF2 Protein uniprot:Q6FHW6

References

  1. Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1. Abdelhak S, Kalatzis V, Heilig R, Compain S, Samson D, Vincent C, et al. Hum Mol Genet. 1997 Dec;6(13):2247–55. PubMed Europe PMC Scholia
  2. Mutations in the SALL1 putative transcription factor gene cause Townes-Brocks syndrome. Kohlhase J, Wischermann A, Reichenbach H, Froster U, Engel W. Nat Genet. 1998 Jan;18(1):81–3. PubMed Europe PMC Scholia
  3. Proteinuria, hypertension and chronic renal failure in X-linked Kallmann’s syndrome, a defined genetic cause of solitary functioning kidney. Duke V, Quinton R, Gordon I, Bouloux PM, Woolf AS. Nephrol Dial Transplant. 1998 Aug;13(8):1998–2003. PubMed Europe PMC Scholia
  4. Anosmin-1 is a regionally restricted component of basement membranes and interstitial matrices during organogenesis: implications for the developmental anomalies of X chromosome-linked Kallmann syndrome. Hardelin JP, Julliard AK, Moniot B, Soussi-Yanicostas N, Verney C, Schwanzel-Fukuda M, et al. Dev Dyn. 1999 May;215(1):26–44. PubMed Europe PMC Scholia
  5. Gdf11 is a negative regulator of chondrogenesis and myogenesis in the developing chick limb. Gamer LW, Cox KA, Small C, Rosen V. Dev Biol. 2001 Jan 15;229(2):407–20. PubMed Europe PMC Scholia
  6. Hoxa 11 is upstream of Integrin alpha8 expression in the developing kidney. Valerius MT, Patterson LT, Feng Y, Potter SS. Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8090–5. PubMed Europe PMC Scholia
  7. Activin type IIA and IIB receptors mediate Gdf11 signaling in axial vertebral patterning. Oh SP, Yeo CY, Lee Y, Schrewe H, Whitman M, Li E. Genes Dev. 2002 Nov 1;16(21):2749–54. PubMed Europe PMC Scholia
  8. Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein. McGregor L, Makela V, Darling SM, Vrontou S, Chalepakis G, Roberts C, et al. Nat Genet. 2003 Jun;34(2):203–8. PubMed Europe PMC Scholia
  9. SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Ruf RG, Xu PX, Silvius D, Otto EA, Beekmann F, Muerb UT, et al. Proc Natl Acad Sci U S A. 2004 May 25;101(21):8090–5. PubMed Europe PMC Scholia
  10. The transcription factor Six2 activates expression of the Gdnf gene as well as its own promoter. Brodbeck S, Besenbeck B, Englert C. Mech Dev. 2004 Oct;121(10):1211–22. PubMed Europe PMC Scholia
  11. Identification of a new gene mutated in Fraser syndrome and mouse myelencephalic blebs. Jadeja S, Smyth I, Pitera JE, Taylor MS, van Haelst M, Bentley E, et al. Nat Genet. 2005 May;37(5):520–5. PubMed Europe PMC Scholia
  12. GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis. Hu MC, Mo R, Bhella S, Wilson CW, Chuang PT, Hui CC, et al. Development. 2006 Feb;133(3):569–78. PubMed Europe PMC Scholia
  13. Breakdown of the reciprocal stabilization of QBRICK/Frem1, Fras1, and Frem2 at the basement membrane provokes Fraser syndrome-like defects. Kiyozumi D, Sugimoto N, Sekiguchi K. Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11981–6. PubMed Europe PMC Scholia
  14. Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: results of the ESCAPE study. Weber S, Moriniere V, Knüppel T, Charbit M, Dusek J, Ghiggeri GM, et al. J Am Soc Nephrol. 2006 Oct;17(10):2864–70. PubMed Europe PMC Scholia
  15. Frem3, a member of the 12 CSPG repeats-containing extracellular matrix protein family, is a basement membrane protein with tissue distribution patterns distinct from those of Fras1, Frem2, and QBRICK/Frem1. Kiyozumi D, Sugimoto N, Nakano I, Sekiguchi K. Matrix Biol. 2007 Jul;26(6):456–62. PubMed Europe PMC Scholia
  16. Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and GDNF/WNT11 feedback signalling during kidney branching morphogenesis. Michos O, Gonçalves A, Lopez-Rios J, Tiecke E, Naillat F, Beier K, et al. Development. 2007 Jul;134(13):2397–405. PubMed Europe PMC Scholia
  17. The ECM protein nephronectin promotes kidney development via integrin alpha8beta1-mediated stimulation of Gdnf expression. Linton JM, Martin GR, Reichardt LF. Development. 2007 Jul;134(13):2501–9. PubMed Europe PMC Scholia
  18. A Hox-Eya-Pax complex regulates early kidney developmental gene expression. Gong KQ, Yallowitz AR, Sun H, Dressler GR, Wellik DM. Mol Cell Biol. 2007 Nov;27(21):7661–8. PubMed Europe PMC Scholia
  19. Fras1, a basement membrane-associated protein mutated in Fraser syndrome, mediates both the initiation of the mammalian kidney and the integrity of renal glomeruli. Pitera JE, Scambler PJ, Woolf AS. Hum Mol Genet. 2008 Dec 15;17(24):3953–64. PubMed Europe PMC Scholia
  20. GLI3 repressor controls nephron number via regulation of Wnt11 and Ret in ureteric tip cells. Cain JE, Islam E, Haxho F, Chen L, Bridgewater D, Nieuwenhuis E, et al. PLoS One. 2009 Oct 7;4(10):e7313. PubMed Europe PMC Scholia
  21. Sprouty1 haploinsufficiency prevents renal agenesis in a model of Fraser syndrome. Pitera JE, Woolf AS, Basson MA, Scambler PJ. J Am Soc Nephrol. 2012 Nov;23(11):1790–6. PubMed Europe PMC Scholia
  22. Urogenital development in Pallister-Hall syndrome is disrupted in a cell-lineage-specific manner by constitutive expression of GLI3 repressor. Blake J, Hu D, Cain JE, Rosenblum ND. Hum Mol Genet. 2016 Feb 1;25(3):437–47. PubMed Europe PMC Scholia
  23. Planar cell polarity genes Celsr1 and Vangl2 are necessary for kidney growth, differentiation, and rostrocaudal patterning. Brzóska HŁ, d’Esposito AM, Kolatsi-Joannou M, Patel V, Igarashi P, Lei Y, et al. Kidney Int. 2016 Dec;90(6):1274–84. PubMed Europe PMC Scholia
  24. Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract. Heidet L, Morinière V, Henry C, De Tomasi L, Reilly ML, Humbert C, et al. J Am Soc Nephrol. 2017 Oct;28(10):2901–14. PubMed Europe PMC Scholia
  25. A Gene Implicated in Activation of Retinoic Acid Receptor Targets Is a Novel Renal Agenesis Gene in Humans. Brophy PD, Rasmussen M, Parida M, Bonde G, Darbro BW, Hong X, et al. Genetics. 2017 Sep;207(1):215–28. PubMed Europe PMC Scholia
  26. Novel Insights into the Pathogenesis of Monogenic Congenital Anomalies of the Kidney and Urinary Tract. van der Ven AT, Vivante A, Hildebrandt F. J Am Soc Nephrol. 2018 Jan;29(1):36–50. PubMed Europe PMC Scholia
  27. Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations. Sanna-Cherchi S, Khan K, Westland R, Krithivasan P, Fievet L, Rasouly HM, et al. Am J Hum Genet. 2017 Nov 2;101(5):789–802. PubMed Europe PMC Scholia
  28. Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice. De Tomasi L, David P, Humbert C, Silbermann F, Arrondel C, Tores F, et al. Am J Hum Genet. 2017 Nov 2;101(5):803–14. PubMed Europe PMC Scholia
  29. Targeted gene sequencing and whole-exome sequencing in autopsied fetuses with prenatally diagnosed kidney anomalies. Rasmussen M, Sunde L, Nielsen ML, Ramsing M, Petersen A, Hjortshøj TD, et al. Clin Genet. 2018 Apr;93(4):860–9. PubMed Europe PMC Scholia
  30. Hedgehog-GLI signaling in Foxd1-positive stromal cells promotes murine nephrogenesis via TGFβ signaling. Rowan CJ, Li W, Martirosyan H, Erwood S, Hu D, Kim YK, et al. Development. 2018 Jul 9;145(13):dev159947. PubMed Europe PMC Scholia