Quantifying the relationship between cell proliferation and morphology during development of the face
Morphogenesis requires highly coordinated, complex interactions between cellular processes: proliferation, migration and apoptosis, along with physical tissue interactions. How these cellular and tissue dynamics drive morphogenesis remains elusive. Three dimensional (3D) microscopic imaging holds great promise, and generates elegant images, but generating even moderate throughput for quantified images is challenging for many reasons. As a result, the association between morphogenesis and cellular processes in 3D developing tissues has not been fully explored. To address this gap, we have developed an imaging and image analysis pipeline to enable 3D quantification of cellular dynamics along with 3D morphology for the same individual embryo. Specifically, we focus on how 3D distribution of proliferation relates to morphogenesis during mouse facial development. Our method involves imaging with light-sheet microscopy, automated segmentation of cells and tissues using machine learning-based tools, and quantification of external morphology by geometric morphometrics. Applying this framework, we show that changes in proliferation are tightly correlated with changes in morphology over the course of facial morphogenesis. These analyses illustrate the potential of this pipeline to investigate mechanistic relationships between cellular dynamics and morphogenesis during embryonic development.
Authors
- Samuel Robertson
- Ralph Marcucio (ORCID: https://orcid.org/0000-0002-0537-818X)
- Sienna Guo
- Lucas Lo Vercio (ORCID: https://orcid.org/0000-0002-5465-6801)
- Benedikt Hallgrímsson (ORCID: https://orcid.org/0000-0002-7192-9103)
- Marta Vidal‐García (ORCID: https://orcid.org/0000-0001-7617-7329)
- Heather L. Szabo‐Rogers (ORCID: https://orcid.org/0000-0002-7921-8031)
- Jay Devine (ORCID: https://orcid.org/0000-0003-0600-1058)
- Arthur D. Lander (ORCID: https://orcid.org/0000-0002-4380-5525)
- Marta Marchini (ORCID: https://orcid.org/0000-0001-5767-5875)
- Nils D. Forkert (ORCID: https://orcid.org/0000-0003-2556-3224)
- Wendy Dean (ORCID: https://orcid.org/0000-0001-9441-5044)
- Rebecca M. Green (ORCID: https://orcid.org/0000-0001-7319-0755)
- Julia C. Boughner (ORCID: https://orcid.org/0000-0003-1147-364X)
- Elizabeth C. Barretto (ORCID: https://orcid.org/0000-0003-1374-6429)
- Andreas Dauter (ORCID: https://orcid.org/0000-0002-5151-6619)
- Anandita Mahika
- Xiang Zhao (ORCID: https://orcid.org/0000-0003-2353-6396)
- M. Bilal Shakir
Institutions
- University of Calgary (CA)
- University of Pittsburgh (US)
- University of California, San Francisco (US)
- University of California, Irvine (US)
- Universitair Ziekenhuis Leuven (BE)
- Alberta Children's Hospital (CA)
- University of Saskatchewan (CA)
- International Craniofacial Institute (US)
- Alberta Bone and Joint Health Institute (CA)
- KU Leuven (BE)
Publication Details
- Journal
- Development
- Published
- 2025-02-24
- DOI
- https://doi.org/10.1242/dev.204511
- Citations
- 2
- Primary Topic
- Cell Image Analysis Techniques
- Type
- article
- Field-Weighted Citation Impact
- 3.27
Funders
- Loyola University Chicago
- University of Pittsburgh
- Children's Hospital Foundation
- Compute Canada
- Western Canada Research Grid
- Universities Space Research Association
- Canada Foundation for Innovation
- Canada Research Chairs
- Alberta Children's Hospital Foundation
- Alberta Innovates
- National Institutes of Health
- University of California, San Francisco
- Alberta Children's Hospital Research Institute
- Cumming School of Medicine, University of Calgary
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- National Institute of Dental and Craniofacial Research
- Institute of Musculoskeletal Health and Arthritis