Investigating the effects of compound paralogous EPHB receptor mutations on mouse facial development.
Investigating the effects of compound paralogous EPHB receptor mutations on mouse facial development.
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研究复合旁系同源EPHB受体突变对小鼠面部发育的影响。
DOI：
10.1002/dvdy.454
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发表时间：
2022-07
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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面部形状的变化可能是由旁系基因的组合或重叠作用引起的。考虑到EPH受体家族成员众多，表达和功能重叠，EPH受体家族是颅面形态变异的一个令人信服的候选来源。我们对E14.5 Ephb1-3受体突变的等位基因系列进行了详细的形态计量学分析，以确定每个旁副受体基因对颅面形态的影响。我们发现Ephb1、Ephb2和Ephb3基因型对面部形状有显著影响，但Ephb1的作用弱于Ephb2和Ephb3的作用。Ephb2−/−和Ephb3−/−突变对面部形态的影响相似，但Ephb3−/−突变对面部形状有额外的影响。整个等位基因序列的颅面差异与预测的加性遗传效应基本一致。然而，我们发现了一个潜在的重要的非加性效应，即Ephb1突变体显示不同的形态，这取决于其他Ephb1亲缘物的组合，其中Ephb1+/−，Ephb1−/−和Ephb1−/−；Ephb3−/−突变体表现出与其预测的面部形状一致的偏差。本研究详细评估了Ephb受体基因同源物对E14.5小鼠面部形态的影响，并展示了特定受体的缺失如何导致面部畸形。
Variation in facial shape may arise from the combinatorial or overlapping actions of paralogous genes. Given its many members, and overlapping expression and functions, the EPH receptor family is a compelling candidate source of craniofacial morphological variation. We performed a detailed morphometric analysis of an allelic series of E14.5 Ephb1-3 receptor mutants to determine the effect of each paralogous receptor gene on craniofacial morphology. We found that Ephb1, Ephb2, and Ephb3 genotypes significantly influenced facial shape, but Ephb1 effects were weaker than Ephb2 and Ephb3 effects. Ephb2−/− and Ephb3−/− mutations affected similar aspects of facial morphology, but Ephb3−/− mutants had additional facial shape effects. Craniofacial differences across the allelic series were largely consistent with predicted additive genetic effects. However, we identified a potentially important non-additive effect where Ephb1 mutants displayed different morphologies depending on the combination of other Ephb paralogs present, where Ephb1+/−, Ephb1−/−, and Ephb1−/−; Ephb3−/− mutants exhibited a consistent deviation from their predicted facial shapes. This study provides a detailed assessment of the effects of Ephb receptor gene paralogs on E14.5 mouse facial morphology and demonstrates how loss of specific receptors contributes to facial dysmorphology.
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