Kidney branching morphogenesis under the control of a ligand-receptor based Turing mechanism

TL;DR

This paper demonstrates that a ligand-receptor based Turing mechanism, specifically involving GDNF-RET interactions, can explain kidney branching morphogenesis and may be a general principle for developmental pattern formation.

Contribution

It extends previous Turing models from lung to kidney development, showing that GDNF-RET interactions can produce realistic branching patterns and protein expression.

Findings

GDNF-RET interaction can generate Turing patterns for kidney branching

The model reproduces wild-type and mutant protein expression patterns

Ligand-receptor Turing mechanisms may be a general principle in development

Abstract

The main signalling proteins that control early kidney branching have been defined. Yet the underlying mechanism is still elusive. We have previously shown that a Schnakenberg-type Turing mechanism can recapitulate the branching and protein expression patterns in wildtype and mutant lungs, but it is unclear whether this mechanism would extend to other branched organs that are regulated by other proteins. Here we show that the GDNF-RET regulatory interaction gives rise to a Schnakenberg-type Turing model that reproduces the observed budding of the ureteric bud from the Wolffian duct, its invasion into the mesenchyme, and the observed branching pattern. The model also recapitulates all relevant protein expression patterns in wild-type and mutant mice. The lung and kidney models are both based on a particular receptor- ligand interaction and require: (1) cooperative binding of ligand and receptor, (2) a lower diffusion coefficient for the receptor than for the ligand, and (3) an increase in the receptor concentration in response to receptor-ligand binding (by enhanced transcription, more recycling or similar). These conditions are met also by other receptor-ligand systems. We propose that ligand-receptor based Turing patterns represent a general mechanism to control branching morphogenesis and other developmental processes.