Embryonic expression of EphA receptor genes in mice supports their candidacy for involvement in cleft lip and palate.
Embryonic expression of EphA receptor genes in mice supports their candidacy for involvement in cleft lip and palate.
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DOI：
10.1002/dvdy.24170
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Bush JO
中科院分区：
文献类型：
--
作者：
Agrawal P;Wang M;Kim S;Lewis AE;Bush JO
Eph受体，包括A-和B-亚家族，是哺乳动物基因组中最大的受体酪氨酸激酶家族，并且它们的功能对于多种环境中的形态发生是至关重要的。尽管已经证明通过B型Ephs的信号传导在唇腭裂（CL/P）中起作用，尽管最近的一项全基因组关联研究将EPHA 3位点确定为非综合征性CL的候选者，但A型Eps的参与尚未在此背景下进行研究。在这里，我们提出了一个系统的分析基因表达模式的九个EphA受体在小鼠发育的进行性阶段，并发现EphA 3，EphA 4和EphA 7在腭发育过程中表现出有限的重叠表达模式。我们发现小鼠中EphA 3的纯合突变或EphA 3和EphA 4的复合纯合突变不会导致有缺陷的面中部发育，支持EphA 7冗余功能的可能性。我们还记录了以前未描述的表达模式在其他组织的颅面复合体，包括泪管和唾液腺。总之，这些结果与EPHA家族基因突变可能导致CL/P的假设一致，也表明家族成员之间的功能冗余可能起作用。
Eph receptors, comprising the A- and B- subfamilies, are the largest family of receptor tyrosine kinases in the mammalian genome, and their function is critical for morphogenesis in a variety of contexts. Whereas signaling through B-type Ephs has been demonstrated to play a role in cleft lip and palate (CL/P), the involvement of A-type Ephs has not been examined in this context notwithstanding a recent genome-wide association study that identified the EPHA3 locus as a candidate for non-syndromic CL/P. Here we present a systematic analysis of the gene expression patterns for the nine EphA receptors at progressive stages of mouse development and find that EphA3, EphA4 and EphA7 exhibit restricted overlapping patterns of expression during palate development. We find that homozygous mutation of EphA3 or compound homozygous mutation of EphA3 and EphA4 in mice does not result in defective midfacial development, supporting the possibility of redundant function with EphA7. We also document previously undescribed expression patterns in other tissues of the craniofacial complex including the lacrimal duct and salivary glands. Together, these results are consistent with the hypothesis that mutations in EPHA family genes may cause CL/P and also suggest that functional redundancy between family members may be at play.
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