Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies.
Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies.
复制标题
从发育，遗传和进化研究中对哺乳动物神经管闭合缺陷的病因的见解。
DOI：
10.3390/jdb6030022
复制
发表时间：
2018-08-21
影响因子：
2.7
通讯作者：
Harris MJ
中科院分区：
文献类型：
--
作者：
Juriloff DM;Harris MJ
人类神经管缺陷（NTD），无脑畸形，脊柱裂和颅脊柱裂，起源于胚胎神经管关闭失败。人类NTD相对常见，遗传起源复杂多样，但其遗传变异和发育机制在很大程度上尚不清楚。在这里，我们回顾了大量的研究，主要是在小鼠中，正常的神经管关闭，失败的机制所造成的特定基因突变，脊椎动物颅神经管的进化及其遗传过程，寻求深入了解人类NTD的病因。我们发现证据的许多地区沿着前后轴每个不同的神经管封闭的形态，细胞行为，所需的特定基因的某些方面，并得出结论，NTD的病因可能是部分特定的前后位置的缺陷，也遗传异质性。我们重新审视了解释小鼠和人类颅骨NTD病例中女性过多的假设，以及了解叶酸途径在NTD中作用的新进展。最后，我们证明，从小鼠突变体的证据强烈支持在人类NTD的所有类型的双基因或寡基因病因的搜索。
The human neural tube defects (NTD), anencephaly, spina bifida and craniorachischisis, originate from a failure of the embryonic neural tube to close. Human NTD are relatively common and both complex and heterogeneous in genetic origin, but the genetic variants and developmental mechanisms are largely unknown. Here we review the numerous studies, mainly in mice, of normal neural tube closure, the mechanisms of failure caused by specific gene mutations, and the evolution of the vertebrate cranial neural tube and its genetic processes, seeking insights into the etiology of human NTD. We find evidence of many regions along the anterior–posterior axis each differing in some aspect of neural tube closure—morphology, cell behavior, specific genes required—and conclude that the etiology of NTD is likely to be partly specific to the anterior–posterior location of the defect and also genetically heterogeneous. We revisit the hypotheses explaining the excess of females among cranial NTD cases in mice and humans and new developments in understanding the role of the folate pathway in NTD. Finally, we demonstrate that evidence from mouse mutants strongly supports the search for digenic or oligogenic etiology in human NTD of all types.