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Computer simulation analysis of normal and abnormal development of the mammalian diaphragm

BioMed Central
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Abstract ral Theoretical Biology and Medical ss BioMed CentModelling Open AcceResearch Computer simulation analysis of normal and abnormal development of the mammalian diaphragm Jason C Fisher1 and Lawrence Bodenstein*1,2 Address: 1Division of Pediatric Surgery, Morgan Stanley Children's Hospital of New York-Presbyterian and Department of Surgery, College of Physicians and Surgeons, Columbia University, 3959 Broadway, 216B, New York, NY 10032, USA and 2Olana Technologies, Inc., 5424 Arlington Avenue, H51, Bronx, NY 10471, USA Email: Jason C Fisher - [email protected]; Lawrence Bodenstein* - [email protected] * Corresponding author Abstract Background: Congenital diaphragmatic hernia (CDH) is a birth defect with significant morbidity and mortality. Knowledge of diaphragm morphogenesis and the aberrations leading to CDH is limited. Although classical embryologists described the diaphragm as arising from the septum transversum, pleuroperitoneal folds (PPF), esophageal mesentery and body wall, animal studies suggest that the PPF is the major, if not sole, contributor to the muscular diaphragm. Recently, a posterior defect in the PPF has been identified when the teratogen nitrofen is used to induce CDH in fetal rodents. We describe use of a cell-based computer modeling system (Nudge++™) to study diaphragm morphogenesis. Methods and results: Key diaphragmatic structures were digitized from transverse serial sections of paraffin-embedded mouse embryos at embryonic days 11.5 and 13. Structure boundaries and simulated cells were combined in the Nudge++™ software. Model cells were assigned putative behavioral programs, and these programs were progressively modified to produce a diaphragm consistent with the observed anatomy in rodents. Homology between our model and recent anatomical observations occurred under the following simulation conditions: (1) cell mitoses are restricted to the edge of growing tissue; (2) cells near the chest wall remain mitotically activ

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