A mathematical model for the induction of the mammalian ureteric bud

Brodie A J Lawson, Mark B Flegg

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)43-56
Number of pages14
JournalJournal of Theoretical Biology
Volume394
DOIs
Publication statusPublished - 7 Apr 2016

Keywords

  • Developmental biology
  • Kidney morphogenesis
  • Mathematical biology
  • Partial differential equations
  • Turing patterning

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