Abstract: TH-OR081

Profiling and Mathematically Modelling Cell and Tissue Morphogenesis during Renal Development

Session Information

Category: Developmental Biology and Inherited Kidney Diseases

  • 401 Developmental Biology

Authors

  • Smyth, Ian, Monash University, Melbourne, New South Wales, Australia
  • Short, Kieran M., Monash University, Melbourne, New South Wales, Australia
  • Lefevre, James, Institute for Molecular Bioscience, The University of Queensland, Highgate Hill, New South Wales, Australia
  • Lamberton, Timothy, The University of Queensland, Brisbane, New South Wales, Australia
  • Combes, Alexander N., University of Melbourne, Parkville, New South Wales, Australia
  • McMahon, Andrew P., Keck School of Medicine of the University of Southern California, Los Angeles, California, United States
  • Little, Melissa H., Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
  • Hamilton, Nicholas A., The University of Queensland, Brisbane, New South Wales, Australia
Background

While cell, tissue and even organism level analyses of morphogenesis are feasible in invertebrates, the size, opacity and complexity of mammalian organs has impeded systematic analyses of developmental processes critical to organ function.

Methods

Here, we integrate optical projection tomography, single-cell resolution confocal microscopy and quantitative image analysis to comprehensively document mouse kidney organogenesis across time. Using mathematical modeling, we develop a framework for generating and comparing modes of branching morphogenesis and compare these models with datasets derived from fetal mouse kidneys.

Results

Our tissue and cell based analysis reveals a previously unappreciated structurally stereotypic organ architecture undergoing a temporally non-uniform process of development with respect to rates of cellular proliferation, dominant morphogenetic processes and spatial relationships between key cellular compartments. Mathematical modelling was able to determine base patterning programs operant in driving branching of the ureteric epithelium, facilitating the analysis of different genetic and morphological impacts on the development of the organ.

Conclusion

Integrating cell, tissue and organ level datasets facilitates quantitative analysis of even subtle perturbations to kidney development and is also applicable to other organ systems. Our data describes a mechanism of branching morphogenesis which is highly patterned when comparing one organ to the next, and across developmental time. The existence of such distinct phases of development and patterning of branching morphogenesis predicts temporal sensitivity to genetic and environmental insults, potentially enhancing our understanding of the mechanism by which developmental anomalies and normal variation in renal anatomy arise.

Funding

  • Government Support - Non-U.S.