3,639 research outputs found
Simulating Organogenesis in COMSOL: Comparison Of Methods For Simulating Branching Morphogenesis
During organogenesis tissue grows and deforms. The growth processes are
controlled by diffusible proteins, so-called morphogens. Many different
patterning mechanisms have been proposed. The stereotypic branching program
during lung development can be recapitulated by a receptor-ligand based Turing
model. Our group has previously used the Arbitrary Lagrangian-Eulerian (ALE)
framework for solving the receptor-ligand Turing model on growing lung domains.
However, complex mesh deformations which occur during lung growth severely
limit the number of branch generations that can be simulated. A new Phase-Field
implementation avoids mesh deformations by considering the surface of the
modelling domains as interfaces between phases, and by coupling the
reaction-diffusion framework to these surfaces. In this paper, we present a
rigorous comparison between the Phase-Field approach and the ALE-based
simulation
Deciphering the Mechanisms of Developmental Disorders (DMDD): a new programme for phenotyping embryonic lethal mice
International efforts to test gene function in the mouse by the systematic knockout of each gene are creating many lines in which embryonic development is compromised. These homozygous lethal mutants represent a potential treasure trove for the biomedical community. Developmental biologists could exploit them in their studies of tissue differentiation and organogenesis; for clinical researchers they offer a powerful resource for investigating the origins of developmental diseases that affect newborns. Here, we outline a new programme of research in the UK aiming to kick-start research with embryonic lethal mouse lines. The 'Deciphering the Mechanisms of Developmental Disorders' (DMDD) programme has the ambitious goal of identifying all embryonic lethal knockout lines made in the UK over the next 5 years, and will use a combination of comprehensive imaging and transcriptomics to identify abnormalities in embryo structure and development. All data will be made freely available, enabling individual researchers to identify lines relevant to their research. The DMDD programme will coordinate its work with similar international efforts through the umbrella of the International Mouse Phenotyping Consortium [see accompanying Special Article (Adams et al., 2013)] and, together, these programmes will provide a novel database for embryonic development, linking gene identity with molecular profiles and morphology phenotypes
Dynamic Image-Based Modelling of Kidney Branching Morphogenesis
Kidney branching morphogenesis has been studied extensively, but the
mechanism that defines the branch points is still elusive. Here we obtained a
2D movie of kidney branching morphogenesis in culture to test different models
of branching morphogenesis with physiological growth dynamics. We carried out
image segmentation and calculated the displacement fields between the frames.
The models were subsequently solved on the 2D domain, that was extracted from
the movie. We find that Turing patterns are sensitive to the initial conditions
when solved on the epithelial shapes. A previously proposed diffusion-dependent
geometry effect allowed us to reproduce the growth fields reasonably well, both
for an inhibitor of branching that was produced in the epithelium, and for an
inducer of branching that was produced in the mesenchyme. The latter could be
represented by Glial-derived neurotrophic factor (GDNF), which is expressed in
the mesenchyme and induces outgrowth of ureteric branches. Considering that the
Turing model represents the interaction between the GDNF and its receptor RET
very well and that the model reproduces the relevant expression patterns in
developing wildtype and mutant kidneys, it is well possible that a combination
of the Turing mechanism and the geometry effect control branching
morphogenesis
Measurement of plant growth in view of an integrative analysis of regulatory networks
As the regulatory networks of growth at the cellular level are elucidated at a fast pace, their complexity is not reduced; on the contrary, the tissue, organ and even whole-plant level affect cell proliferation and expansion by means of development-induced and environment-induced signaling events in growth regulatory processes. Measurement of growth across different levels aids in gaining a mechanistic understanding of growth, and in defining the spatial and temporal resolution of sampling strategies for molecular analyses in the model Arabidopsis thaliana and increasingly also in crop species. The latter claim their place at the forefront of plant research, since global issues and future needs drive the translation from laboratory model-acquired knowledge of growth processes to improvements in crop productivity in field conditions
Digit patterning during limb development as a result of the BMP-receptor interaction
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
- …