Bayesian inference of agent-based models: a tool for studying kidney branching morphogenesis
Authored by Alexander G Fletcher, Helen M Byrne, Ben Lambert, Adam L MacLean, Alexander N Combes, Melissa H Little
Date Published: 2018
DOI: 10.1007/s00285-018-1208-z
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Abstract
The adult mammalian kidney has a complex, highly-branched collecting
duct epithelium that arises as a ureteric bud sidebranch from an
epithelial tube known as the nephric duct. Subsequent branching of the
ureteric bud to form the collecting duct tree is regulated by
subcellular interactions between the epithelium and a population of
mesenchymal cells that surround the tips of outgrowing branches. The
mesenchymal cells produce glial cell-line derived neurotrophic factor
(GDNF), that binds with RET receptors on the surface of the epithelial
cells to stimulate several subcellular pathways in the epithelium. Such
interactions are known to be a prerequisite for normal branching
development, although competing theories exist for their role in
morphogenesis. Here we introduce the first agent-based model of ex vivo
kidney uretic branching. Through comparison with experimental data, we
show that growth factor-regulated growth mechanisms can explain early
epithelial cell branching, but only if epithelial cell division depends
in a switch-like way on the local growth factor concentration; cell
division occurring only if the driving growth factor level exceeds a
threshold. We also show how a recently-developed method, ``Approximate
Approximate Bayesian Computation{''}, can be used to infer key model
parameters, and reveal the dependency between the parameters controlling
a growth factor-dependent growth switch. These results are consistent
with a requirement for signals controlling proliferation and chemotaxis,
both of which are previously identified roles for GDNF.
Tags
epithelium
Cellular automaton
Migration
morphology
systems
growth
Mechanisms
Computation
Tumor-growth
In-vitro
Protein
Organogenesis
Developmental processes
Mathematical
modelling
Ureteral bud morphogenesis
Wolffian duct
Gdnf
Quantification
Ureteral bud outgrowth