Open Access Data for, "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 in skull morphogenesis is not well studied and it remains an enigmatic structure. We provide complete three-dimensional (3D) reconstructions of the laboratory mouse chondrocranium from embryonic day 13.5 through 17.5 using a novel methodology of uncertainty-guided segmentation of phosphotungstic enhanced 3D microcomputed 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 the 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.

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Work Title Open Access Data for, "A dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocranium"
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Open Access
Creators
  1. Susan M. Motch Perrine
  2. Mary Kathleen Pitirri
  3. Joan Richtsmeier
Keyword
  1. craniofacial development
  2. skull
  3. embryonic cartilage
  4. Crouzon syndrome
  5. FGFR
  6. fibroblast growth factor
License CC BY 4.0 (Attribution)
Work Type Article
Acknowledgments
  1. We would like to thank Dr. Jacob Eswarakumar for the gift of the Fgfr2cC342Y/+ Crouzon mouse model.
Publication Date November 25, 2021
DOI doi:10.26207/qgke-r185
Related URLs
Deposited February 10, 2022

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Version 1
published

  • Created
  • Updated Keyword, Related URLs Show Changes
    Keyword
    • craniofacial development
    • craniofacial development, skull, embryonic cartilage, Crouzon syndrome, FGFR, fibroblast growth factor
    Related URLs
    • https://www.biorxiv.org/content/10.1101/2021.11.24.469914v1
  • Added Creator Susan M. Motch Perrine
  • Added Creator Mary Kathleen Pitirri
  • Added Creator Joan Richtsmeier
  • Added README.txt
  • Added Crouzon_Fgfr2c_C342Y_chondrocrania.zip
  • Updated License Show Changes
    License
    • https://creativecommons.org/licenses/by-nc-nd/4.0/
  • Published
  • Updated

Version 2
published

  • Created
  • Updated Work Title, Description Show Changes
    Work Title
    • 3D reconstructions of Crouzon Fgfr2c C342Y Mouse Chondrocrania Models
    • Open Access Data for, "A dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocranium"
    Description
    • The cranial endo- and dermal skeletons, which comprise the vertebrate skull, evolved independently and form separately during embryogenesis. In mammals, the mostly cartilaginous cranial endoskeleton forms prior to the bony dermatocranium. Many features of the chondrocranium are transient, undergoing endochondral ossification or disappearing, so its role in skull morphogenesis is not understood The fibroblast growth factor (FGF) and receptor (FGFR) signaling pathway contributes significantly to the regulation of osteochondroprogenitor cell function. Mutations in FGFR genes are associated with diseases that impact the skull including dwarfing chondrodyplasia and craniosynostosis syndromes. We investigate the developing chondrocranium and dermatocranium using a mouse model for craniosynostosis carrying a gain of function mutation in Fgfr2 to assess development of these cranial skeleton systems. Dermatocrania and chondrocrania of Fgfr2cC342Y/+ mice and their Fgfr2c+/+ littermates were quantified in 3D from microcomputed tomography images of mouse embryos. Chondrocrania of embryonic mice carrying the Fgfr2 mutation are larger than their Fgfr2c+/+ littermates and include novel extensions of cartilage over the lateral and dorsal aspect of the brain. Like the forming chondrocranium, the embryonic dermatocranium is larger in Fgfr2cC342Y/+ mice throughout embryogenesis but after disappearance of much of the chondrocranium, the dermatocranium becomes progressively smaller relative to Fgfr2c+/+ littermates during postnatal growth. Results reveal the direct effects of this Fgfr2c mutation on embryonic cranial cartilage, the impact of chondrocranial structure on developing dermatocranial elements, the importance of the chondrocranium in decoding the impact of specific genetic variants on head morphogenesis, and the potential for harnessing these effects as therapeutic targets.
    • 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 three-dimensional (3D) reconstructions of the laboratory mouse chondrocranium from embryonic day 13.5 through 17.5 using a novel methodology of uncertainty-guided segmentation of phosphotungstic enhanced 3D microcomputed tomography images with sparse annotation. We evaluate the embryonic mouse chondrocranium and dermatocranium in 3D and delineate the effects of a <I>Fgfr2</I> variant on embryonic chondrocranial cartilages and on the association with forming dermal bones using the <I>Fgfr2c<SUP>C342Y/+</SUP> </I>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 <I>Fgfr2 </I>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 <I>Fgfr2c<SUP>C342Y/+ </SUP></I>embryos at all timepoints before the chondrocranium begins to disintegrate at E16.5. The chondrocrania and forming dermatocrania of <I>Fgfr2c<SUP>C342Y/+ </SUP></I>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 <I>Fgfr2c<SUP>C342Y/+</SUP></I> mice reduced in most dimensions compared to <I>Fgfr2c<SUP>+/+ </SUP></I>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.
  • Added Main_README.txt
  • Updated License Show Changes
    License
    • https://creativecommons.org/licenses/by-nc-nd/4.0/
    • https://creativecommons.org/licenses/by/4.0/
  • Added PCA_data.zip
  • Added Morphological_Integration.zip
  • Added Landmark_data.zip
  • Added Bone_volumes.zip
  • Added Bone_microCT_docs.zip
  • Added Bone_microCT_P0.zip
  • Added PTA_microCT_docs.zip
  • Added Bone_microCT_P2.zip
  • Added Histology_images_and_spreadsheets.zip
  • Added PTA_microCT_E13.5.zip
  • Added PTA_microCT_E17.5.zip
  • Added PTA_microCT_E15.5.zip
  • Added PTA_microCT_E16.5.zip
  • Added PTA_microCT_E14.5.zip
  • Added Bone_microCT_E17.5.zip
  • Added Bone_microCT_E15.5.zip
  • Added Bone_microCT_E16.5.zip
  • Deleted README.txt
  • Deleted Main_README.txt
  • Added README.txt
  • Updated Description Show Changes
    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 three-dimensional (3D) reconstructions of the laboratory mouse chondrocranium from embryonic day 13.5 through 17.5 using a novel methodology of uncertainty-guided segmentation of phosphotungstic enhanced 3D microcomputed tomography images with sparse annotation. We evaluate the embryonic mouse chondrocranium and dermatocranium in 3D and delineate the effects of a <I>Fgfr2</I> variant on embryonic chondrocranial cartilages and on the association with forming dermal bones using the <I>Fgfr2c<SUP>C342Y/+</SUP> </I>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 <I>Fgfr2 </I>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 <I>Fgfr2c<SUP>C342Y/+ </SUP></I>embryos at all timepoints before the chondrocranium begins to disintegrate at E16.5. The chondrocrania and forming dermatocrania of <I>Fgfr2c<SUP>C342Y/+ </SUP></I>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 <I>Fgfr2c<SUP>C342Y/+</SUP></I> mice reduced in most dimensions compared to <I>Fgfr2c<SUP>+/+ </SUP></I>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.
    • 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 three-dimensional (3D) reconstructions of the laboratory mouse chondrocranium from embryonic day 13.5 through 17.5 using a novel methodology of uncertainty-guided segmentation of phosphotungstic enhanced 3D microcomputed 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 the association with forming dermal bones using the *Fgfr2c<SUP>C342Y/+</SUP> *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 *Fgfr2c<SUP>C342Y/+ </SUP>*embryos at all timepoints before the chondrocranium begins to disintegrate at E16.5. The chondrocrania and forming dermatocrania of *Fgfr2c<SUP>C342Y/+ </SUP>*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 *Fgfr2c<SUP>C342Y/+</SUP>* mice reduced in most dimensions compared to *Fgfr2c<SUP>+/+ </SUP>*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.
  • Deleted README.txt
  • Added README.txt
  • Published

Version 3
published

  • Created
  • Updated Description Show Changes
    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 three-dimensional (3D) reconstructions of the laboratory mouse chondrocranium from embryonic day 13.5 through 17.5 using a novel methodology of uncertainty-guided segmentation of phosphotungstic enhanced 3D microcomputed 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 the association with forming dermal bones using the *Fgfr2c<SUP>C342Y/+</SUP> *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 *Fgfr2c<SUP>C342Y/+ </SUP>*embryos at all timepoints before the chondrocranium begins to disintegrate at E16.5. The chondrocrania and forming dermatocrania of *Fgfr2c<SUP>C342Y/+ </SUP>*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 *Fgfr2c<SUP>C342Y/+</SUP>* mice reduced in most dimensions compared to *Fgfr2c<SUP>+/+ </SUP>*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.
    • 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 three-dimensional (3D) reconstructions of the laboratory mouse chondrocranium from embryonic day 13.5 through 17.5 using a novel methodology of uncertainty-guided segmentation of phosphotungstic enhanced 3D microcomputed 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 the association with forming dermal bones using the *Fgfr2c<SUP>C342Y/+</SUP>* 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 *Fgfr2c<SUP>C342Y/+ </SUP>* embryos at all timepoints before the chondrocranium begins to disintegrate at E16.5. The chondrocrania and forming dermatocrania of *Fgfr2c<SUP>C342Y/+ </SUP>* 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 *Fgfr2c<SUP>C342Y/+</SUP>* mice reduced in most dimensions compared to *Fgfr2c<SUP>+/+ </SUP>* 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.
  • Updated Related URLs Show Changes
    Related URLs
    • https://www.biorxiv.org/content/10.1101/2021.11.24.469914v1
    • https://www.biorxiv.org/content/10.1101/2021.11.24.469914v1, https://www.biorxiv.org/content/10.1101/2021.11.24.469914v2
  • Updated Acknowledgments Show Changes
    Acknowledgments
    • We would like to thank Dr. Jacob Eswarakumar for the gift of the Fgfr2cC342Y/+ Crouzon mouse model.
  • Published