Expression of Gdnf in metanephric mesenchyme

Stable Identifier
R-MMU-9830744
Type
Reaction [omitted]
Species
Mus musculus
Compartment
nucleoplasm, extracellular region
ReviewStatus
3/5
General
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Expression of Gdnf in metanephric mesenchyme
Glial cell line-derived neurotrophic factor (Gdnf) is expressed in the metanephric mesenchyme during formation of the ureteric bud (Hellmich et al. 1996, Pichel et al. 1996, Sainio et al. 1997, Towers et al. 1998). Gdnf, which is secreted from the metanephric mesenchyme, interacts with the Ret receptor tyrosine kinase on the nephric duct to regulate induction of the ureteric bud (Sainio et al. 1997, Pepicelli et al. 1997, Towers et al. 1998, Chi et al. 2009). The interaction between Nephronectin (Npnt) secreted by the nephric duct and Integrin alpha8/beta1 (Itga8) expressed on metanephric mesenchyme cells enhances the expression of Gdnf (Linton et al. 2007). Based on phenotypes of knockouts, Slit2 and Robo2 appear to repress Gdnf expression to limit the size of the ureteric bud (Grieshammer et al. 2004), however this may be an indirect effect produced by the activity of Slit2:Robo2 in producing normal physical separation of the mesenchyme from the Wolffian duct and ureteric epithelium (Wainwright et al. 2015). Mice lacking Gdnf fail to develop kidneys (Pichel et al. 1996).
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
17785448 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
8657307 Defects in enteric innervation and kidney development in mice lacking GDNF

Pichel, JG, Shen, L, Sheng, HZ, Granholm, AC, Drago, J, Grinberg, A, Lee, EJ, Huang, SP, Saarma, M, Hoffer, BJ, Sariola, H, Westphal, H

Nature 1996
8808409 Embryonic expression of glial cell-line derived neurotrophic factor (GDNF) suggests multiple developmental roles in neural differentiation and epithelial-mesenchymal interactions

Hellmich, HL, Kos, L, Cho, ES, Mahon, KA, Zimmer, A

Mech Dev 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
9374404 Glial-cell-line-derived neurotrophic factor is required for bud initiation from ureteric epithelium

Sainio, K, Suvanto, P, Davies, J, Wartiovaara, J, Wartiovaara, K, Saarma, M, Arumäe, U, Meng, X, Lindahl, M, Pachnis, V, Sariola, H

Development 1997
15130495 SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site

Grieshammer, U, Ma, L, Plump, AS, Wang, F, Tessier-Lavigne, M, Martin, GR

Dev Cell 2004
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
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
12050119 Hox11 paralogous genes are essential for metanephric kidney induction

Wellik, DM, Hawkes, PJ, Capecchi, MR

Genes Dev 2002
Participants
Input
Output
This event is regulated
Negatively by
Regulator
Foxc1 [nucleoplasm] (Mus musculus)
Regulator
Robo2:Slit2 [plasma membrane] (Mus musculus)
Regulator
Foxc2 [nucleoplasm] (Mus musculus)
Positively by
Regulator
Npnt:Itga8:Itgb1 [plasma membrane] (Mus musculus)
Regulator
Eya1:Pax2:Hox11 paralog:Gdnf gene [nucleoplasm] (Mus musculus)
Active Unit
Eya1 [nucleoplasm]
Pax2 [nucleoplasm]
Hox11 paralog [nucleoplasm]
Regulator
N4GlycoAsn-PalmS Wnt11 [extracellular region] (Mus musculus)
Orthologous Events
Expression of GDNF in metanephric mesenchyme (Homo sapiens)
Authored
May, B  (2023-03-13)
Created
May, B  (2023-03-14)
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