13 - Early embryonic morphology of brains and chondrocrania in the Fgfr2+/P253R mouse model of Apert Syndrome
Monday, March 25, 2024
10:15am – 12:15pm US EDT
Location: Sheraton Hall
Poster Board Number: 13
There are separate poster presentation times for odd and even posters.
Odd poster #s – first hour
Even poster #s – second hour
Co-authors:
Jordan Wilson - Department of Anthropology - Pennsylvania State University; Frederick Foster - Department of Anthropology - Pennsylvania State University; Yuhan Hsi - Department of Anthropology - Pennsylvania State University; Mizuho Kawasaki - Department of Anthropology - Pennsylvania State University; Joan Richtsmeier - Department of Anthropology - Pennsylvania University; Kazuhiko Kawazaki - Department of Anthropology - Pennsylvania State University; Susan Motch Perrine - Department of Anthropology - Pennsylvania State University
Research Assistant Pennsylvania State University marlton, New Jersey, United States
Abstract Body : Apert Syndrome (AS), a craniosynostosis syndrome resulting from mutations in the fibroblast growth factor receptor 2 (FGFR2) gene, is characterized by premature closure of cranial sutures, dysmorphology of the skull, brain malformation and limb abnormalities. Less well studied are changes in the chondrocranium that develops as the cartilaginous skeleton of the head. In mice, the chondrocranium forms in sequence beginning at embryonic day 12.5 (E12.5) and serves as the protective covering for the brain and other sense organs. The chondrocranium is subsequently resorbed and replaced by the dermatocranium that develops by intramembranous ossification or undergoes endochondral ossification to form the bones of the skull. To provide a detailed understanding of the structure of the chondrocranium, we characterized how the FGFR2:p.Pro253Arg mutation, causative for approximately 33% of AS cases in children, affects brain and chondrocranial morphology using the Fgfr2+/P253R mouse model of AS. We acquired phosphotungstic acid enhanced micro-computed tomography (PTAe microCT) images of six E14.5 Fgfr2+/P253Rspecimens and four Fgfr2+/+ unaffected littermates. Following segmentation of our PTAe microCT images for cartilage, which used sparse annotation to train our automatic deep learning based three-dimensional (3D) segmentation model, 3D isosurfaces were created for the chondrocrania. Thirteen biologically relevant anatomical landmarks were collected twice on each chondrocranium by the same observer and corrected for errors. Additionally, eight anatomically relevant brain landmarks were collected on the PTAe microCT slice images by the same procedure. Using linear distances estimated from 3D coordinates of the collected landmarks for each structure, we discovered statistically significant morphological differences in both the chondrocranium and brain in Fgfr2+/P253R specimens as compared to their Fgfr2+/+ unaffected littermates. Our results indicated a lateral expansion of the chondrocranial cartilages that will later form the ethmoid bone and provide support to the ventral areas of the olfactory bulbs and cerebral cortex. Additionally, there was a suggestion of lateral expansion of the cerebral cortex and a reduction in lateral expansion of the cerebellum in Fgfr2+/P253R specimens as compared to their Fgfr2+/+ unaffected littermates. Our data show direct effects of Fgfr2 mutations on embryonic chondrocrania and brains. These effects may later impact cranial bone development, which will be explored in future.