Formation of the ureteric bud

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R-HSA-9830674
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Pathway
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Homo sapiens
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3/5
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Formation of the ureteric bud
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Visible kidney development initiates with the formation of the pronephros and then the mesonephros (reviewed in McMahon 2016). In amniotes these are transitory structures that are superseded by formation of the metanephros, the functional kidney that persists into adulthood. The nephric duct appears during development of the pronephros and then extends caudally in the mesonephros, inducing the formation of mesonephric tubules that drain into the nephric duct and provide blood filtration in the embryo. (The mesonephric duct is also called the Wolffian duct.)
Subsequently, the metanephros is initiated by formation of the ureteric bud in the nephric duct due to the interaction between the nephric duct and the adjacent metanephric mesenchyme. The ureteric bud will grow to become the ureter, branch further, and induce the formation of nephrons and collecting ducts at the termini of the branches (reviewed in Costantini 2012). Development of the ureteric bulge is regulated by reciprocal signals passed between the nephric duct and the metanephric mesenchyme (reviewed in Marcotte et al. 2014). Nephronectin (NPNT) secreted by the nephric duct interacts with Integrin alpha8/beta1 (ITGA8) on the metanephric mesenchyme to activate expression of GDNF in the metanephric mesenchyme (Brandenberger et al. 2001, Linton et al. 2007). GDNF secreted by the metanephric mesenchyme then binds and activates the RET tyrosine kinase located in the plasma membrane of nephric duct cells (Trupp et al. 1996, Majumdar et al. 2003). RET activates expression of WNT11 in the nephric duct to regulate differentiation (Majumdar et al. 2003). The extent of kidney development is circumscribed by inhibitory signals provided by ROBO2:SLIT at the duct-mesenchyme interface (Wainwright et al. 2015) and by FOXC1,2 from the paraxial mesoderm.
Literature References
PubMed ID Title Journal Year
17537792 The ECM protein nephronectin promotes kidney development via integrin alpha8beta1-mediated stimulation of Gdnf expression

Linton, JM, Martin, GR, Reichardt, LF

Development 2007
24104595 Gene regulatory network of renal primordium development

Marcotte, M, Sharma, R, Bouchard, M

Pediatr Nephrol 2014
8657281 Functional receptor for GDNF encoded by the c-ret proto-oncogene

Trupp, M, Arenas, E, Fainzilber, M, Nilsson, AS, Sieber, BA, Grigoriou, M, Kilkenny, C, Salazar-Grueso, E, Pachnis, V, Arumäe, U

Nature 1996
11470831 Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin alpha8beta1 in the embryonic kidney

Brandenberger, R, Schmidt, A, Linton, J, Wang, D, Backus, C, Denda, S, Müller, U, Reichardt, LF

J Cell Biol 2001
22942910 Genetic controls and cellular behaviors in branching morphogenesis of the renal collecting system

Costantini, F

Wiley Interdiscip Rev Dev Biol 2012
12783789 Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development

Majumdar, A, Vainio, S, Kispert, A, McMahon, J, McMahon, AP

Development 2003
26116176 ROBO2 restricts the nephrogenic field and regulates Wolffian duct-nephrogenic cord separation

Wainwright, EN, Wilhelm, D, Combes, AN, Little, MH, Koopman, P

Dev Biol 2015
26969971 Development of the Mammalian Kidney

McMahon, AP

Curr Top Dev Biol 2016
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Go Biological Process
ureteric bud formation (0060676)
Authored
May, B  (2023-03-12)
Created
May, B  (2023-03-13)
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