A dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocranium
The cranial endo and dermal skeletons, which comprise the vertebrate skull, evolved independently over 470 million years ago and form separately during embryogenesis. In mammals, much of the cartilaginous chondrocranium is transient, undergoing endochondral ossification or disappearing, so its role...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/76653 |
| _version_ | 1828221071943270400 |
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| author | Susan M Motch Perrine M Kathleen Pitirri Emily L Durham Mizuho Kawasaki Hao Zheng Danny Z Chen Kazuhiko Kawasaki Joan T Richtsmeier |
| author_facet | Susan M Motch Perrine M Kathleen Pitirri Emily L Durham Mizuho Kawasaki Hao Zheng Danny Z Chen Kazuhiko Kawasaki Joan T Richtsmeier |
| author_sort | Susan M Motch Perrine |
| collection | DOAJ |
| description | The cranial endo and dermal skeletons, which comprise the vertebrate skull, evolved independently over 470 million years ago and form separately during embryogenesis. In mammals, much of the cartilaginous chondrocranium is transient, undergoing endochondral ossification or disappearing, so its role in skull morphogenesis is not well studied and it remains an enigmatic structure. We provide complete 3D reconstructions of the laboratory mouse chondrocranium from embryonic day (E) 13.5 through E17.5 using a novel methodology of uncertainty-guided segmentation of phosphotungstic enhanced 3D micro-computed tomography images with sparse annotation. We evaluate the embryonic mouse chondrocranium and dermatocranium in 3D, and delineate the effects of a Fgfr2 variant on embryonic chondrocranial cartilages and on their association with forming dermal bones using the Fgfr2cC342Y/+ Crouzon syndrome mouse. We show that the dermatocranium develops outside of and in shapes that conform to the chondrocranium. Results reveal direct effects of the Fgfr2 variant on embryonic cartilage, on chondrocranium morphology, and on the association between chondrocranium and dermatocranium development. Histologically, we observe a trend of relatively more chondrocytes, larger chondrocytes, and/or more matrix in the Fgfr2cC342Y/+ embryos at all timepoints before the chondrocranium begins to disintegrate at E16.5. The chondrocrania and forming dermatocrania of Fgfr2cC342Y/+ embryos are relatively large, but a contrasting trend begins at E16.5 and continues into early postnatal (P0 and P2) timepoints, with the skulls of older Fgfr2cC342Y/+ mice reduced in most dimensions compared to Fgfr2c+/+ littermates. Our findings have implications for the study and treatment of human craniofacial disease, for understanding the impact of chondrocranial morphology on skull growth, and potentially on the evolution of skull morphology. |
| first_indexed | 2024-04-12T16:35:18Z |
| format | Article |
| id | doaj.art-06e8edb056c64da1949281a466cadacd |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:35:18Z |
| publishDate | 2022-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-06e8edb056c64da1949281a466cadacd2022-12-22T03:25:00ZengeLife Sciences Publications LtdeLife2050-084X2022-06-011110.7554/eLife.76653A dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocraniumSusan M Motch Perrine0https://orcid.org/0000-0003-3412-221XM Kathleen Pitirri1Emily L Durham2https://orcid.org/0000-0002-6322-9393Mizuho Kawasaki3Hao Zheng4https://orcid.org/0000-0002-9790-7607Danny Z Chen5https://orcid.org/0000-0001-6565-2884Kazuhiko Kawasaki6https://orcid.org/0000-0003-1090-5340Joan T Richtsmeier7https://orcid.org/0000-0002-0239-5822Department of Anthropology, The Pennsylvania State University, University Park, United StatesDepartment of Anthropology, The Pennsylvania State University, University Park, United StatesDepartment of Anthropology, The Pennsylvania State University, University Park, United StatesDepartment of Anthropology, The Pennsylvania State University, University Park, United StatesDepartment of Computer Science and Engineering, University of Notre Dame, Notre Dame, United StatesDepartment of Computer Science and Engineering, University of Notre Dame, Notre Dame, United StatesDepartment of Anthropology, The Pennsylvania State University, University Park, United StatesDepartment of Anthropology, The Pennsylvania State University, University Park, United StatesThe cranial endo and dermal skeletons, which comprise the vertebrate skull, evolved independently over 470 million years ago and form separately during embryogenesis. In mammals, much of the cartilaginous chondrocranium is transient, undergoing endochondral ossification or disappearing, so its role in skull morphogenesis is not well studied and it remains an enigmatic structure. We provide complete 3D reconstructions of the laboratory mouse chondrocranium from embryonic day (E) 13.5 through E17.5 using a novel methodology of uncertainty-guided segmentation of phosphotungstic enhanced 3D micro-computed tomography images with sparse annotation. We evaluate the embryonic mouse chondrocranium and dermatocranium in 3D, and delineate the effects of a Fgfr2 variant on embryonic chondrocranial cartilages and on their association with forming dermal bones using the Fgfr2cC342Y/+ Crouzon syndrome mouse. We show that the dermatocranium develops outside of and in shapes that conform to the chondrocranium. Results reveal direct effects of the Fgfr2 variant on embryonic cartilage, on chondrocranium morphology, and on the association between chondrocranium and dermatocranium development. Histologically, we observe a trend of relatively more chondrocytes, larger chondrocytes, and/or more matrix in the Fgfr2cC342Y/+ embryos at all timepoints before the chondrocranium begins to disintegrate at E16.5. The chondrocrania and forming dermatocrania of Fgfr2cC342Y/+ embryos are relatively large, but a contrasting trend begins at E16.5 and continues into early postnatal (P0 and P2) timepoints, with the skulls of older Fgfr2cC342Y/+ mice reduced in most dimensions compared to Fgfr2c+/+ littermates. Our findings have implications for the study and treatment of human craniofacial disease, for understanding the impact of chondrocranial morphology on skull growth, and potentially on the evolution of skull morphology.https://elifesciences.org/articles/76653craniofacial developmentskullembryonic cartilageCrouzon syndromeFGFRintramembranous ossification |
| spellingShingle | Susan M Motch Perrine M Kathleen Pitirri Emily L Durham Mizuho Kawasaki Hao Zheng Danny Z Chen Kazuhiko Kawasaki Joan T Richtsmeier A dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocranium eLife craniofacial development skull embryonic cartilage Crouzon syndrome FGFR intramembranous ossification |
| title | A dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocranium |
| title_full | A dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocranium |
| title_fullStr | A dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocranium |
| title_full_unstemmed | A dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocranium |
| title_short | A dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocranium |
| title_sort | dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocranium |
| topic | craniofacial development skull embryonic cartilage Crouzon syndrome FGFR intramembranous ossification |
| url | https://elifesciences.org/articles/76653 |
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