Opitz John M
Departments of Pediatrics (Medical Genetics), Human Genetics, Pathology, Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah.
Am J Med Genet A. 2016 Oct;170(10):2503-22. doi: 10.1002/ajmg.a.37810. Epub 2016 Jul 15.
The investigation of mammalian malformations began to approach human needs in the 19th century with, for example, Meckel's dissection of sibs with the "Meckel" syndrome, his intimation of Heredität as cause of the condition, his conclusion as to the common causal origin of this specific combination of congenital anomalies, the clear enunciation of the concept of primary malformations, the recognition that many human malformations are normal developmental states in other animals, and that some were normal anatomical states in remote ancestors and now still normal in collateral descendants (atavisms, Darwin's "reversions"; for example, four wings in dipterans, normal in dragonflies and their common ancestor). Later in the century, Wilhelm His Sr. had proposed a schematic map of "organ-forming districts" for prospective chick development, a concept that did not sit well with early workers in developmental biology (e.g., Boveri) until methods became available for a direct experimental "attack" on the embryo. This approach was pioneered by Spemann and Mangold through interspecies transplantation of embryonic rudiments with the spectacular result that set the research stage in developmental biology for the next many years. But it was not until mid-century that the late, great geneticist, Curt Stern, made the His model of chick development more intellectually and experimentally approachable with his meticulous analysis of cuticular appendages of Drosophila, one bristle and one bristle group (field) at a time, in mosaics or gynandromorphs, leading to the ingenious concept of prepatterns. As a basic scientist, Stern did not broaden prepatterns into medicine or to human malformations where it has now found a most gratifying application. This contribution to the Carey Festschrift is to summarize, briefly, field and prepattern theory. © 2016 Wiley Periodicals, Inc.
19世纪,哺乳动物畸形的研究开始贴近人类需求,例如,梅克尔对患有“梅克尔”综合征的同胞进行解剖,暗示遗传是病因,得出这种先天性异常特定组合的共同病因起源,明确阐述原发性畸形的概念,认识到许多人类畸形在其他动物中是正常发育状态,有些在远古祖先中是正常解剖状态,现在在旁系后代中仍然正常(返祖现象,达尔文的“回复”;例如,双翅目昆虫的四翅,在蜻蜓及其共同祖先中是正常的)。在该世纪后期,老威廉·希斯提出了一份预期鸡胚胎发育的“器官形成区”示意图,这一概念在发育生物学早期工作者(如博韦里)中并不受欢迎,直到有方法可对胚胎进行直接实验“研究”。这种方法由施佩曼和曼戈尔德开创,他们通过种间移植胚胎原基取得了惊人成果,为接下来许多年的发育生物学研究奠定了基础。但直到本世纪中叶,已故的伟大遗传学家柯特·斯特恩通过对果蝇表皮附属物进行细致分析,一次研究一根刚毛和一个刚毛组(区域),在嵌合体或雌雄嵌合体中进行研究,提出了巧妙的预模式概念,才使希斯的鸡胚胎发育模型在理论和实验上更易于理解。作为一名基础科学家,斯特恩并未将预模式概念扩展到医学或人类畸形领域,而如今预模式概念在这些领域有了非常令人满意的应用。本文对《凯里纪念文集》的贡献是简要总结区域和预模式理论。© 2016威利期刊公司