  The development of long bones requires a sophisticated spatial organization
of cellular signaling, proliferation, and differentiation programs. How such
spatial organization emerges on the growing long bone domain is still
unresolved. Based on the reported biochemical interactions we developed a
regulatory model for the core signaling factors IHH, PTCH1, and PTHrP and
included two cell types, proliferating/resting chondrocytes and
(pre-)hypertrophic chondrocytes. We show that the reported IHH-PTCH1
interaction gives rise to a Schnakenberg-type Turing kinetics, and that
inclusion of PTHrP is important to achieve robust patterning when coupling
patterning and tissue dynamics. The model reproduces relevant spatiotemporal
gene expression patterns, as well as a number of relevant mutant phenotypes. In
summary, we propose that a ligand-receptor based Turing mechanism may control
the emergence of patterns during long bone development, with PTHrP as an
important mediator to confer patterning robustness when the sensitive Turing
system is coupled to the dynamics of a growing and differentiating tissue. We
have previously shown that ligand-receptor based Turing mechanisms can also
result from BMP-receptor and GDNF-receptor interactions, and that these
reproduce the wildtype and mutant patterns during digit formation in limbs and
branching morphogenesis in lung and kidneys. Receptor-ligand interactions may
thus constitute a general mechanism to generate Turing patterns in nature.
