Midline craniofacial malformations with a lipomatous cephalocele are associated with insufficient closure of the neural tube in the tuft mouse.
Midline craniofacial malformations with a lipomatous cephalocele are associated with insufficient closure of the neural tube in the tuft mouse.
复制标题
伴有脂肪瘤性头膨出的中线颅面畸形与簇状小鼠神经管闭合不充分有关。
DOI：
10.1002/bdra.23264
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Lozanoff,Scott
中科院分区：
文献类型：
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作者：
Fong,KeithSK;Adachi,DanaAT;Chang,ShaunB;Lozanoff,Scott
背景影响头部神经管闭合的遗传变异会导致面部和大脑畸形，对医疗保健费用和生活质量造成重大影响。方法我们从野生型群体中自发产生的突变建立了小鼠系，我们称之为簇。簇状小鼠具有遗传性中线颅面缺陷，特征是前部脂肪瘤性头膨出。结果整体骨骼染色表明受影响的新生儿具有更广泛的特征。额间缝，头膨出出现在额骨之间。头膨出位于讲台附近的小鼠也出现颅面畸形，例如眼距离过远和鼻中面部裂。肉眼和组织学检查显示，脂肪瘤性头膨出起源于不早于E14.5的充满液体的囊肿，而在E11.5的颅面发育过程中，具有中面裂的胚胎是明显的。具有中面裂的胚胎的组织学切片显示，头神经外胚层仍然接近或与前神经孔闭合部位周围的额鼻外胚层融合，表明神经管闭合存在缺陷。我们发现E9至E10.5胚胎的喙部神经皱襞向内卷曲且未能闭合，以及后期的外脑畸形和无脑畸形胚胎。前部标记物 Fgf8 和 Sonic hedgehog 的整体原位杂交表明，在严重的情况下，嘴位点的闭合受到损害。结论我们提出了一个模型，展示了神经管闭合缺陷后如何产生前颅头膨出以及与随后的颅面形态发生的相关性。出生缺陷研究（A 部分）100:598–607，2014 年。© 2014 Wiley periodicals, Inc.
BackgroundGenetic variations affecting neural tube closure along the head result in malformations to the face and brain, posing a significant impact on health care costs and the quality of life.MethodsWe have established a mouse line from a mutation that arose spontaneously in our wild‐type colony that we calledtuft.Tuftmice have heritable midline craniofacial defects featuring an anterior lipomatous cephalocele.ResultsWhole‐mount skeletal stains indicated that affected newborns had a broader interfrontal suture where the cephalocele emerged between the frontal bones. Mice with a cephalocele positioned near the rostrum also presented craniofacial malformations such as ocular hypertelorism and midfacial cleft of the nose. Gross and histological examination revealed that the lipomatous cephalocele originated as a fluid filled cyst no earlier than E14.5 while embryos with a midfacial cleft was evident during craniofacial development at E11.5. Histological sections of embryos with a midfacial cleft revealed the cephalic neuroectoderm remained proximal or fused to the frontonasal ectoderm about the closure site of the anterior neuropore, indicating a defect to neural tube closure. We found the neural folds along the rostrum of E9 to E10.5 embryos curled inward and failed to close as well as embryos with exencephaly and anencephaly at later stages. Whole‐mount in situ hybridization of anterior markers Fgf8 and Sonic hedgehog indicated closure of the rostral site was compromised in severe cases.ConclusionWe present a model demonstrating how anterior cranial cephaloceles are generated following a defect to neural tube closure and relevance to subsequent craniofacial morphogenesis in thetuftmouse. Birth Defects Research (Part A) 100:598–607, 2014. © 2014 Wiley Periodicals, Inc.