The Hectd1 ubiquitin ligase is required for development of the head mesenchyme and neural tube closure
The Hectd1 ubiquitin ligase is required for development of the head mesenchyme and neural tube closure
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DOI：
10.1016/j.ydbio.2007.03.018
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发表时间：
2007-06-01
影响因子：
2.7
通讯作者：
Niswander, Lee
中科院分区：
文献类型：
--
作者：
Zohn, Irene E.;Anderson, Kathryn V.;Niswander, Lee
颅神经管的闭合依赖于头部间充质的正常发育。ENU诱导的开放心智(OPM)突变的纯合子突变胚胎表现出与头部间充质发育缺陷和背侧铰链点形成相关的脑外畸形。OPM突变型胚胎的头部间充质较野生型胚胎致密，细胞结构异常。由于起源于头旁轴中胚层和神经脊的细胞充填于头部间充质，我们探讨了异常头部间充质的起源。OPM突变型胚胎表现出神经脊源性结构的明显正常发育。此外，OPM突变胚胎中异常的珠间充质不是来源于神经脊，而是表达头部中胚层的分子标记。我们还报告了在普遍表达的Hectd1E3泛素连接酶中OPM突变的鉴定。两个不同的Hectd1等位基因导致杂合子动物的不完全穿透性神经管缺陷，表明Hectd1功能在神经管关闭的临界阈值上是必需的。Hectd1突变杂合子胚胎中神经管缺陷的外显率低，提示Hectd1基因可作为人类神经管缺陷的候选易感基因。(C)2007 Elsevier Inc.保留所有权利。
Closure of the cranial neural tube depends on normal development of the head mesenchyme. Homozygous-mutant embryos for the ENU-induced open mind (opm) mutation exhibit exencephaly associated with defects in head mesenchyme development and dorsal-lateral hinge point formation. The head mesenchyme in opm mutant embryos is denser than in wildtype embryos and displays an abnormal cellular organization. Since cells that originate from both the cephalic paraxial mesoderm and the neural crest populate the head mesenchyme, we explored the origin of the abnormal head mesenchyme. opm mutant embryos show apparently normal development of neural crest-derived structures. Further-more, the abnormal bead mesenchyme in opm mutant embryos is not derived from the neural crest, but instead expresses molecular markers of cephalic mesoderm. We also report the identification of the opm mutation in the ubiquitously expressed Hectd1 E3 ubiquitin ligase. Two different Hectd1 alleles cause incompletely penetrant neural tube defects in heterozygous animals, indicating that Hectd1 function is required at a critical threshold for neural tube closure. This low penetrance of neural tube defects in embryos heterozygous for Hectd1 mutations suggests that Hectd1 should be considered as candidate susceptibility gene in human neural tube defects. (C) 2007 Elsevier Inc. All rights reserved.