A dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocranium.
A dysmorphic mouse model reveals developmental interactions of chondrocranium and dermatocranium.
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DOI：
10.7554/elife.76653
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发表时间：
2022-06-15
期刊：
影响因子：
7.7
通讯作者：
Zhu, Min
中科院分区：
文献类型：
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作者：
Motch Perrine, Susan M.;Pitirri, M. Kathleen;Durham, Emily L.;Kawasaki, Mizuho;Zheng, Hao;Chen, Danny Z.;Kawasaki, Kazuhiko;Richtsmeier, Joan T.;Zhu, Min
关键词：
构成脊椎动物头骨的颅内骨骼和真皮骨骼在4.7亿多年前独立进化，并在胚胎发育过程中单独形成。在哺乳动物中，大部分软骨性软骨颅骨是暂时的，经历软骨内骨化或消失，因此其在颅骨形态发生中的作用没有得到很好的研究，它仍然是一个谜。我们提供了完整的三维重建实验室小鼠软骨颅骨从胚胎天（E）13.5通过E17.5使用一种新的方法不确定性引导分割磷钨增强三维微计算机断层扫描图像稀疏注释。我们评估了胚胎小鼠软骨颅和皮颅的三维，并描绘了Fgfr 2变体对胚胎软骨颅软骨的影响，以及它们与使用Fgfr 2cC 342 Y/+ Crouzon综合征小鼠形成真皮骨的关系。我们发现皮颅在软骨颅外发育，其形状与软骨颅一致。结果揭示了Fgfr 2变体对胚胎软骨、软骨颅形态以及软骨颅和皮颅发育之间的关联的直接影响。在组织学上，我们观察到在软骨颅在E16.5开始崩解之前的所有时间点，Fgfr 2cC 342 Y/+胚胎中相对更多软骨细胞、更大软骨细胞和/或更多基质的趋势。Fgfr 2cC 342 Y/+胚胎的软骨颅和形成性皮颅相对较大，但相反的趋势始于E16.5，并持续到出生后早期（P0和P2）时间点，与Fgfr 2c +/+同窝仔相比，年龄较大的Fgfr 2cC 342 Y/+小鼠的头骨在大多数尺寸上减小。我们的研究结果对人类颅面疾病的研究和治疗，了解软骨颅形态对颅骨生长的影响，并可能对颅骨形态的演变产生影响。
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.
影响因子：
--
作者：
Liu J;Kwon TG;Nam HK;Hatch NE
通讯作者：
Hatch NE