Digit patterning during limb development as a result of the BMP-receptor interaction

TL;DR

This paper demonstrates that BMP-receptor interactions can produce Turing patterns, explaining digit formation during limb development through a molecular mechanism consistent with experimental data.

Contribution

It shows that BMP-receptor interactions can generate Schnakenberg-type Turing patterns, providing a molecular basis for digit patterning in limb development.

Findings

Model reproduces wildtype and mutant expression patterns

BMP-receptor interaction meets Turing pattern conditions

Patterning explained on realistic limb bud domain

Abstract

Turing models have been proposed to explain the emergence of digits during limb development. However, so far the molecular components that would give rise to Turing patterns are elusive. We have recently shown that a particular type of receptor-ligand interaction can give rise to Schnakenberg-type Turing patterns, which reproduce patterning during lung and kidney branching morphogenesis. Recent knock-out experiments have identified Smad4 as a key protein in digit patterning. We show here that the BMP-receptor interaction meets the conditions for a Schnakenberg-type Turing pattern, and that the resulting model reproduces available wildtype and mutant data on the expression patterns of BMP, its receptor, and Fgfs in the apical ectodermal ridge (AER) when solved on a realistic 2D domain that we extracted from limb bud images of E11.5 mouse embryos. We propose that receptor-ligand-based mechanisms serve as a molecular basis for the emergence of Turing patterns in many developing tissues.