IDENTIFICATION OF GENES REGULATING THE DEVELOPMENT OF EMBRYONIC LIMB BUDS

建立模式形成所必需的基因的鉴定 在形态发生过程中，研究它们的调节与 脊椎动物生物学的许多方面。 形态发生中的许多关键过程， 包括对营养刺激、细胞-细胞相互作用、迁移 差异增殖、程序性细胞死亡等，概括了 在肿瘤发生过程中以病理方式发生。 因此， 在形态发生过程中活跃的过程，它们的调节最终将 有助于更好地理解肿瘤发生的机制， 转移，并可能提供深入了解癌症预防和治疗 战略布局 鸡肢发育是一个很有吸引力的研究系统 图案形成的分子基础，因为在 组织/细胞相互作用的水平已经被很好地表征， 与哺乳动物非常相似，这个系统很容易适应 生物化学和分子分析以及显微外科操作。 该项目的目的是分离调控形态发生的基因， 鸡胚肢芽。 目前正在制定两种办法： 产生富集了潜在的调节基因的消减cDNA文库 和诱导基因;和2）鉴定相关/新成员 与发育有关的保守基因家族 其他系统中的监管程序。 同源异型盒的两个新成员 已经鉴定了一些基因家族，它们显示出空间限制性， 在肢芽内的表达域，表明在调节 沿着前后（A-P）和近远侧（proximodistal）的图案形成 (P-D)肢体的轴。 其中一个基因也表达在 早期胚胎在原肠胚形成期间，以及肢芽，并可能 规范沿着主要 胚胎轴，以及肢体P-D轴。 研究正在进行中， 阐明这些调控基因的功能，使用两种分子 遗传和生物化学方法。

The identification of genes necessary for establishing pattern formation during morphogenesis and the study of their regulation are relevant to many aspects of vertebrate biology. Many key processes in morphogenesis, including responses to trophic stimuli, cell-cell interactions, migration, differential proliferation, programmed cell death, etc., are recapitulated in a pathologic manner during oncogenesis. So, an understanding of processes active during morphogenesis and their regulation will ultimately contribute to a better understanding of mechanisms of oncogenesis and metastasis, and may provide insight into cancer prevention and treatment strategies. Chick limb development is an attractive system for studying the molecular basis of pattern formation because critical events at the level of tissue/cellular interactions have been well characterized and are very similar to those in mammals, and this system is readily amenable to biochemical and molecular analysis as well as microsurgical manipulation. The aim of this project is to isolate genes that regulate morphogenesis in the chick embryo limb bud. Two approaches are being developed: 1) the generation of subtracted cDNA libraries enriched for potential regulatory and induced genes; and 2) the identification of related/new members of conserved gene families that have been implicated in developmental regulatory processes in other systems. Two novel members of the homeobox gene family have been identified which show spatially restricted expression domains within the limb bud that suggest roles in regulating pattern formation along the anterior-posterior (A-P) and the proximodistal (P-D) axes of the limb. One of these genes is also expressed in the very early embryo during gastrulation, as well as the limb bud, and may regulate the determination of positional identity along the primary embryonic axis, as well as the limb P-D axis. Studies are underway to elucidate the function of these regulatory genes, using both molecular genetic and biochemical approaches.