Hall B K
J Craniofac Genet Dev Biol. 1987;7(2):145-59.
Mandibular development was examined in embryonic chicks following administration of 5-fluoro-2'-deoxyuridine (FUDR, 0.001-1.0 microgram/egg), an inhibitor of both DNA synthesis and of cell division. FUDR was injected in ovo at one of three developmental stages corresponding to 1) the migration of mandible-destined, midbrain-level neural crest cells (Hamburger and Hamilton [H.H.] stage 10); 2) midway through the epithelial-mesenchymal interaction required to initiate mandibular osteogenesis (H.H. stage 22), which is also after the epithelial-neural crest cell interaction required for the initiation of chondrogenesis in Meckel's cartilage; and 3) when prechondroblasts of Meckel's cartilage are beginning to differentiate (H.H. stage 25). Micromelia was induced following the administration of FUDR at either H.H. stages 22 or 25 but not when FUDR was given at H.H. stage 10. Although the micromelic mandibles were shorter than normal, Meckel's cartilage and the mandibular membrane bones both differentiated and grew along the full proximodistal length of the shortened mandibles. In contrast to the situation previously described by Ferguson for alligator embryos exposed to FUDR, the migration of neural crest cells in the embryonic chick was not inhibited by FUDR. In contrast to the situation previously described for rat embryos exposed to FUDR, differentiation of Meckel's cartilage was not inhibited in embryonic chicks exposed to FUDR. Differentiation of the membrane bones was also normal following either in ovo administration of FUDR or when mandibular processes were maintained in FUDR in vitro. Therefore, FUDR does not produce micromelia in the embryonic chick by interfering with the epithelial-mesenchymal/neural crest cell interactions, which are prerequisites or differentiation of cartilage or bone, nor by inhibiting the differentiation of chondrogenic or osteogenic mesenchymal cells after completion of these tissue interactions. Neither did the growth-inhibiting action of FUDR result from an inhibition of growth of Meckel's cartilage during the several days following initial chondrogenic differentiation. Rather, subsequent growth of the entire mandibular process was delayed. This mechanism of action differs from that in the alligator embryo, in which FUDR inhibits mandibular growth by removing mandible-destined, migrating neural crest cells, and in the rat, in which FUDR inhibits the differentiation of Meckel's cartilage but catch-up growth restores growth of the mandible to normal.
在给胚胎小鸡注射5-氟-2'-脱氧尿苷（FUDR，0.001 - 1.0微克/蛋）后，对其下颌骨发育进行了研究。FUDR是一种DNA合成和细胞分裂的抑制剂。在三个发育阶段之一对胚胎小鸡进行卵内注射FUDR，这三个阶段分别对应于：1）下颌骨定向的中脑水平神经嵴细胞迁移时（汉伯格和汉密尔顿[H.H.]第10阶段）；2）启动下颌骨成骨所需的上皮-间充质相互作用进行到一半时（H.H.第22阶段），这也是梅克尔软骨软骨生成启动所需的上皮-神经嵴细胞相互作用之后；3）梅克尔软骨的前软骨细胞开始分化时（H.H.第25阶段）。在H.H.第22或25阶段注射FUDR后诱导出了短肢畸形，但在H.H.第10阶段注射FUDR时未出现。虽然短肢畸形的下颌骨比正常的短，但梅克尔软骨和下颌骨膜性骨都沿着缩短的下颌骨的整个近远中长度进行了分化和生长。与弗格森之前描述的暴露于FUDR的短吻鳄胚胎的情况不同，FUDR并未抑制胚胎小鸡中神经嵴细胞的迁移。与之前描述的暴露于FUDR的大鼠胚胎的情况不同，暴露于FUDR的胚胎小鸡中梅克尔软骨的分化未受抑制。在卵内注射FUDR或在下颌突在体外培养于FUDR中时，膜性骨的分化也正常。因此，FUDR在胚胎小鸡中不会通过干扰上皮-间充质/神经嵴细胞相互作用（这是软骨或骨分化的前提条件），也不会通过在这些组织相互作用完成后抑制软骨生成或成骨间充质细胞的分化来产生短肢畸形。FUDR的生长抑制作用也不是由于在最初的软骨生成分化后的几天内抑制了梅克尔软骨的生长。相反，整个下颌突的后续生长被延迟了。这种作用机制与短吻鳄胚胎不同，在短吻鳄胚胎中，FUDR通过去除下颌骨定向的迁移神经嵴细胞来抑制下颌骨生长；与大鼠也不同，在大鼠中，FUDR抑制梅克尔软骨的分化，但追赶生长使下颌骨恢复正常生长。
