SITE-SPECIFIC MALFORMATIONS IN THE EMBRYO

来自各种动物的证据表明， 在神经传递发育之前的形态发生中发挥作用。 为 例如，鸡胚中的研究证明了摄取和/或 5-羟色胺（5-HT）和去甲肾上腺素（NE）的合成 管和脊索，以及药物干扰的吸收，合成或 这些物质的代谢产生神经系统的畸形 系统 在小鼠中，这类药物引起类似的畸形，但没有 研究还没有进行，以确定是否存在5-HT或NE网站 在这个或其他哺乳动物物种，这可以提供一个很好的模型， 药物诱发人类畸形的研究。 初步 研究，使用小鼠胚胎的全胚胎培养，我们已经确定 5-HT摄取和/或合成的位点，通过将胚胎与5-HT或 前体，然后用免疫细胞化学染色固定切片， 5-HT的抗血清 使用这种方法，我们已经定位5-HT摄取 发育中的心脏、头部外胚层、骨骺、下颌骨和 咽弓、腭、耳囊（耳）和尾侧下的后肠 神经管关闭时。 利用整个胚胎培养体系， 我建议研究这些5-羟色胺网站方面1）他们的发展 时间进程和药理学特征，以及2）作为潜在病灶 5-HT相互作用药物的致畸作用。 可能的形态发生学 我们有抗血清的其他神经递质的作用（例如， 儿茶酚胺和GABA）也将使用相同的体外检测 我们将首先探索摄取和/或合成的位点 然后测试合适的药物是否有致畸作用。 这些 研究应提供关于以下方面作用的新信息： 神经递质在形态发生中的作用， 精神药物可能导致的特定部位畸形 被孕妇带走了。

Evidence from a variety of animal species suggests that neurotransmitters play roles in morphogenesis prior to development of neurotransmission. For example, studies in the chick embryo demonstrate sites of uptake and/or synthesis for serotonin (5-HT) and norepinephrine (NE) in the early neural tube and notochord, and drugs which interfere with the uptake, synthesis or metabolism of these substances produce malformations of the nervous system. In the mouse, such drugs cause similar malformations, but no studies have yet been conducted to determine whether 5-HT or NE sites exist in this or other mammalian species, which could provide a good model for studies of drug-induced malformations in the human. In preliminary studies, using whole embryo culture of mouse embryos, we have identified sites of 5-HT uptake and/or synthesis by incubation of embryos with 5-HT or precursors followed by immunocytochemical staining of fixed sections with an antiserum to 5-HT. Using this approach, we have localized 5-HT uptake sites in the developing heart, head ectoderm, epiphysis, mandibular and pharyngeal arches, palate, otocyst (ear), and hindgut underlying the caudal neural tube during closure. Using the whole embryo culture system, we propose to study these 5-HT sites in terms of 1) their developmental timecourse and pharmacologic characterization, and 2) as potential foci for teratogenic effects of 5-HT-interactive drugs. The possible morphogenetic roles of other neurotransmitters for which we have antisera (e.g., catecholamines and GABA) will also be examined using the same in vitro approach in which we will first explore sites of uptake and/or synthesis and then test appropriate drugs for related teratogenic effects. These studies should produce new information regarding roles for neurotransmitters in morphogenesis as well as providing valuable insights into possible site-specific malformations caused by psychoactive drugs taken by the pregnant woman.