GENES DIFFERENTIALLY EXPRESSED IN DEVELOPING EMBRYONIC LIMB BUDS

建立模式所必需的基因的鉴定 形态发生过程中的形成及其调控研究 这些问题是脊椎动物生物学许多方面的核心问题。许多 形态发生的关键过程，包括对营养刺激的反应， 细胞间的相互作用、迁移、差异细胞增殖、 程序性细胞死亡等，在病理上也有概括 在肿瘤发生过程中的作用方式。雏鸡肢体发育是一种诱人的 用于研究图案形成的分子基础的系统，因为 组织/细胞相互作用水平上的关键事件 花纹的形成已经被很好地刻画了，看起来非常 与哺乳动物系统中的类似，而且这个系统很容易 适用于生化和分子分析以及显微外科手术 操纵。 这项长期计划的目标是分离出 调控鸡胚肢芽的形态发生。两位将军 正在开发的方法：1)产生消减的cdna 丰富潜在调控和诱导基因的文库；以及2) 鉴定保守基因家族的相关/新成员 与其他发育调控过程有牵连 系统。目前，同源异型盒基因家族的两个新成员 已鉴定出哪些基因在早期有选择地在肢芽中表达 发展。其中一个基因是以分级的方式表达的 四肢的A-P轴，翼芽比腿芽更丰富， 暗示在图案形成和/或确定中可能扮演的角色 肢体类型的同一性。第二个基因似乎是选择性的 在发育后的肢芽中表达，可能在以后的发育中发挥作用 形态发生事件，如重塑。目前正在进行研究，以 阐明这些调控基因的功能，使用遗传学和 生化方法。

The identification of genes necessary for establishing pattern formation during morphogenesis and the study of their regulation are problems which are central to many aspects of vertebrate biology. Many key processes in morphogenesis, including responses to trophic stimuli, cell-cell interactions, migration, differential cell multiplication, programmed cell death, etc., are also recapitulated in a pathologic manner during oncogenesis. 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 involved in pattern formation have been well characterized and appear to be very similar to those in mammalian systems, and this system is readily amenable to biochemical and molecular analysis as well as microsurgical manipulation. It is the aim of this long-term project to isolate genes that regulate morphogenesis in the chick embryo limb bud. Two general 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. Currently, two new members of the homeobox gene family have been identified which are selectively expressed in limb buds during early development. One of these genes is expressed in a graded fashion along the A-P axis of the limb and is more abundant in wing than leg buds, suggesting possible roles in pattern formation and/or the determination of limb-type identity. The second gene appears to be selectively expressed later in developing limb buds and might play a role in later morphogenetic events such as remodeling. Studies are underway to elucidate the function of these regulatory genes, using both genetic and biochemical approaches.