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Computational Model of Secondary Palate Fusion and Disruption ChemResTox Data

Metadata Updated: May 2, 2021

Morphogenetic events are driven by cell-generated physical forces and complex cellular dynamics. To improve our capacity to predict developmental effects from cellular alterations, we built a multi-cellular agent-based model in CompuCell3D that recapitulates the cellular networks and collective cell behavior underlying growth and fusion of the mammalian secondary palate. The model incorporated multiple signaling pathways (TGF?, BMP, FGF, EGF, SHH) in a biological framework to recapitulate morphogenetic events from palatal outgrowth through midline fusion. It effectively simulated higher-level phenotypes (e.g., midline contact, medial edge seam (MES) breakdown, mesenchymal confluence, fusion defects) in response to genetic or environmental perturbations. Perturbation analysis of various control features revealed model functionality with respect to cell signaling systems and feedback loops for growth and fusion, diverse individual cell behaviors and collective cellular behavior leading to physical contact and midline fusion, and quantitative analysis of the TGF/EGF switch that controls MES breakdown – a key event in morphogenetic fusion. The virtual palate model was then executed with theoretical chemical perturbation scenarios to simulate switch behavior leading to a disruption of fusion following chronic (e.g., dioxin) and acute (e.g., retinoic acid, hydrocortisone) toxicant exposures. This computer model adds to similar systems models toward a ‘virtual embryo’ for simulation and quantitative prediction of adverse developmental outcomes following genetic perturbation and/or environmental.

This dataset is associated with the following publication: Hutson, S., M. Leung, N. Baker, R. Spencer, and T. Knudsen. (CHEMICAL RESEARCH IN TOXICOLOGY) Computational Model of Secondary Palate Fusion and Disruption. CHEMICAL RESEARCH IN TOXICOLOGY. American Chemical Society, Washington, DC, USA, 30(4): 965-979, (2017).

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Public: This dataset is intended for public access and use. License: See this page for license information.

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Metadata Created Date November 12, 2020
Metadata Updated Date May 2, 2021

Metadata Source

Harvested from EPA ScienceHub

Additional Metadata

Resource Type Dataset
Metadata Created Date November 12, 2020
Metadata Updated Date May 2, 2021
Publisher U.S. EPA Office of Research and Development (ORD)
Data Last Modified 2017-09-26
Public Access Level public
Bureau Code 020:00
Schema Version
Harvest Object Id 53db2d39-dc15-47a7-93cb-b9c4ce05d87a
Harvest Source Id 04b59eaf-ae53-4066-93db-80f2ed0df446
Harvest Source Title EPA ScienceHub
Program Code 020:095
Publisher Hierarchy U.S. Government > U.S. Environmental Protection Agency > U.S. EPA Office of Research and Development (ORD)
Related Documents
Source Datajson Identifier True
Source Hash 670d3cb86a2224c4c238e54aad7fc721418dd091
Source Schema Version 1.1

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