A mathematical model for the induction of the mammalian ureteric bud

• Presented is a mathematical model for the chemical kinetics of kidney induction.
• We validate a Turing mechanism for the creation of a single ureteric bud.
• Our model predicts various developmental phenotypes observed in genetic experiments.
• A role of Gremlin is to stabilise single bud induction against fluctuations in BMP.

Congenital abnormalities of the kidney and urinary tract collectively form the most common type of prenatally diagnosed malformations. Whilst many of the crucial genes that direct the kidney developmental program are known, the mechanisms by which kidney organogenesis is achieved is still largely unclear. In this paper, we propose a mathematical model for the localisation of the ureteric bud, the precursor to the ureter and collecting duct system of the kidney. The mathematical model presented fundamentally implicates Schnakenberg-like ligand-receptor Turing patterning as the mechanism by which the ureteric bud is localised on the Wolfian duct as proposed by Menshykaul and Iber (2013). This model explores the specific roles of regulatory proteins GREM1 and BMP as well as the domain properties of GDNF production. Our model demonstrates that this proposed pattern formation mechanism is capable of naturally predicting the phenotypical outcomes of many genetic experiments from the literature. Furthermore, we conclude that whilst BMP inhibits GDNF away from the budding site and GREM1 permits GDNF to signal, GREM1 also stabilises the effect of BMP on GDNF signalling from fluctuations in BMP sensitivity but not signal strength.