The interplay of genetic and environmental factors in craniofacial morphogenesis: Holoprosencephaly and the role of cholesterol.
The interplay of genetic and environmental factors in craniofacial morphogenesis: Holoprosencephaly and the role of cholesterol.
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DOI：
10.1111/j.1741-4520.2003.tb01022.x
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发表时间：
2003-03-01
影响因子：
1.3
通讯作者：
Muenke, Maximilian
中科院分区：
文献类型：
--
作者：
Edison, Robin;Muenke, Maximilian
独眼畸形，严重前脑无裂畸形（HPE）中典型的“脸（预测大脑）”（DeMyer等人，1964年），自古以来就被公认。描述性胚胎学家和病理学家已经注意到连续的前脑分离缺陷和中枢神经系统（CNS）中线结构丢失超过世纪。最近人们认识到，胆固醇生物合成的抑制剂，无论是绵羊食用的本地植物，还是实验性地应用于早期胚胎，都可以复制自然畸形的表型，就像各种其他致畸剂一样（母亲糖尿病，酒精）。然而，不到十年的时间，基因组知识库和强大的分析方法已经将描述性科学、分子学和遗传胚胎学带入了彼此的范围。本文就HPE的临床表现及发病机制作一综述。我们将概述导致HPE的各种遗传和致畸机制。最后，我们将尝试研究胆固醇和Sonic Hedgehog（Shh）通路在这种疾病和正常胚胎前脑发育中的关键作用。“如果大脑是如此简单，我们可以理解它，我们会如此简单，我们不能。"
Cyclopia, the paradigmatic "face (that) predicts the brain" in severe holoprosencephaly (HPE) (DeMyer et al., 1964), has been recognized since ancient times. Descriptive embryologists and pathologists have noted the continuum of defective separation of the forebrain and loss of central nervous system (CNS) midline structures for more than a century. It has been recognized more recently that inhibitors of cholesterol biosynthesis, whether consumed in native plants by range sheep, or experimentally applied to early embryos, could phenocopy the natural malformation, as could a variety of other teratogens (maternal diabetes, alcohol). Yet it has been less than a decade that the genomic knowledge base and powerful analytic methods have brought the sciences of descriptive, molecular, and genetic embryology within range of each other. In this review, we discuss the clinical presentations and pathogenesis of HPE. We will outline various genetic and teratogenic mechanisms leading to HPE. Lastly, we will attempt to examine the pivotal role of cholesterol and the Sonic Hedgehog (Shh) pathway in this disorder and in normal embryonic forebrain development. "If the brain were so simple that we could understand it, we'd be so simple, we couldn't."