A dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocranium

Area of Science:

• Developmental Biology
• Evolutionary Biology
• Genetics

Background:

• The vertebrate skull comprises endo- and dermal skeletons, evolving independently over 470 million years ago.
• The mammalian embryonic chondrocranium is transient and enigmatic, with its role in skull morphogenesis poorly understood.
• Craniofacial development is crucial for understanding congenital anomalies and evolutionary processes.

Purpose of the Study:

• To reconstruct and analyze the embryonic mouse chondrocranium and dermatocranium in 3D.
• To investigate the effects of a fibroblast growth factor receptor 2 (Fgfr2) variant on chondrocranial development and its association with dermal bone formation.
• To provide insights into the mechanisms underlying craniofacial development and disease.

Main Methods:

• Novel uncertainty-guided segmentation of micro-computed tomography images for 3D reconstruction.
• Analysis of the embryonic mouse chondrocranium and dermatocranium from embryonic day (E) 13.5 to E17.5.
• Histological evaluation of chondrocytes and matrix in wild-type and Fgfr2c Crouzon syndrome mouse embryos.

Main Results:

• The dermatocranium develops externally, conforming to the chondrocranium's shape.
• The Fgfr2 variant directly impacts embryonic cartilage, chondrocranium morphology, and chondrocranium-dermatocranium interactions.
• Fgfr2c embryos show altered chondrocranium and dermatocranium size during development, with later postnatal skull reduction.

Conclusions:

• The chondrocranium plays a significant role in shaping the skull, influencing dermatocranium development.
• Fgfr2 signaling is critical for normal chondrocranium and dermatocranium development and their integration.
• Findings have implications for understanding and treating human craniofacial diseases and skull evolution.