Gradients and the Control of Pattern Formation

;​R等于E等于F。C o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o= ?@ A B C D E F G F Microsoft Word 6.0文档MSWordDoc。6;(((( : 噢,书商旧体（轻）（TT） BriemScript (TT) Playbill (TT) Book Antiqua (TT) Braggadocio (TT) Peignot Medium（中）（TT） Arial Narrow （TT）书商旧体（DemiBold斜体）（TT） Parade (TT) Times Bell MT (TT) Onyx (TT 9513550 Small现代生物学的一个中心问题是遗传信息如何在高等真核生物中建立体型。在果蝇中，身体计划的建立涉及到一系列分割基因的协调活动，这些基因沿着前后轴建立了重复片段的模板，而同源基因则指定了每个片段的身份。在分割层次结构的每一步中，基因表达模式都有显著的改进，最终在14行单细胞横行模式中表达片段极性基因，这将产生未来的片段边界细胞。这种改进的最引人注目的例子是从间隙基因的广泛表达域到成对规则基因的异聚条纹模式的转变。最近的分子分析表明，这种转变涉及间隙基因编码的蛋白质产物与成对规则基因的顺式调控区域（增强子）的直接DNA结合。尽管已经花费了大量的精力来阐明这些相互作用中涉及的增强子的结构，但是对模式的反式控制所知相对较少。然而，有假设认为间隙蛋白可能作为分级形态因子，以浓度依赖的方式控制成对规则基因的活性。间隙基因在确定同源基因的表达位置方面也起着至关重要的作用，这对于确定发育后期单个片段的身份非常重要。本文概述了一系列实验，旨在直接测试间隙基因在分割过程中形态发生的梯度模型，以及同源基因在片段规范中的作用。在这些研究中，将采用遗传分析和间接错表达技术相结合的方法来精确地改变胚皮中的间隙和同源基因表达模式。错表达实验将利用均匀跳过基因的条带2增强子来控制异位表达的位置和时间。通过操纵这种增强子中已知的结合位点，可以非常精确地改变异位表达的形状和水平。初步结果表明，缺口基因的错误表达会导致片段表达模式的中断，这与形态发生的梯度机制一致。令人惊讶的是，在胚胎发生过程中，这种破坏不会造成致命，许多个体突变体存活到蛹形成的后期。因此，这里提出的实验不仅可以分析胚胎基因如何相互作用以形成更精细的表达模式，而且还可以分析这些模式如何控制对幼虫和成体形成重要的细胞命运决定。*** ;Oh +' 0 $ H l D H R:\WWUSER\TEMPLATE\NORMAL。你是我的朋友，我是你的朋友，我是你的朋友，我是你的朋友。9513550 eozsaruh eozsaruh @ @ @ @ @ @ f# Microsoft Word 6.0;e = e a a j j j j j j j j j 1 1 e T + 4 j 4 j j jjj ~ jjjjj。[9513550小]现代生物学的一个中心问题是如何

; R o o t E n t r y F , C o m p O b j b W o r d D o c u m e n t O b j e c t P o o l = ? @ A B C D E F G F Microsoft Word 6.0 Document MSWordDoc Word.Document.6 ; (((( :ll: flffl xhh``` llllf xh00hx hl =P u P Z Bookman Old Style (Light) (TT) BriemScript (TT) Playbill (TT) Book Antiqua (TT) Braggadocio (TT) Peignot Medium (Medium) (TT) Arial Narrow (TT) Bookman Old Style (DemiBold Italic) (TT) Parade (TT) Times Bell MT (TT) Onyx (TT 9513550 Small A central question in modern biology is how genetic information establishes body form in higher eukaryotes. In Drosophila, the establishment of the body plan involves the coordinate activities of a hierarchy of segmentation genes, which establish a template of reiterated segments along the anterior-posterior axis, and homeotic genes, which specify the identity of each segment. At every step in the segmentation hierarchy, there are significant refinements in patterns of gene expression that culminate in the expression of the segment polarity genes in patterns of fourteen transverse rows of single cells that will give rise to the future border cells of the segments. The most dramatic example of such a refinement is seen in the transition from the broad expression domains of the gap genes to the metameric striped patterns of the pair-rule genes. Recent molecular analyses suggest that this transition involves direct DNA binding of the protein products encoded by the gap genes to the cis regulatory regions (enhancers) of the pair-rule genes. Although much effort has been expended eluc idating the structure of the enhancers involved in these interactions, relatively little is known about the trans control of the patterns. However, it has been hypothesized that gap proteins may act as graded morphogens to control pair-rule gene activity in a concentration dependent manner. The gap genes also play a crucial role in establishing the positions of expression of the homeotic genes, which are important for specifying the identity of individual segments later in development. This proposal outlines a series of experiments designed to directly test the gradient model of morphogenesis for gap genes during segmentation, and the role of the homeotic genes in segmental specification. In these studies, a combination of genetic analyses and indirect misexpression techniques will be performed to precisely alter gap and homeotic gene expression patterns in the blastoderm. The misexpression experiments will use the well characterized stripe 2 enhancer from the even-skipped gene to control the position and timing of ectopic expression. By manipulating known binding sites in this enhancer, the shape and level of ectopic expression can be changed in a very precise way. Preliminary results suggest that misexpressing the gap gene, knirps causes disruptions in segmentation expression patterns that are consistent with a gradient mechanism of morphogenesis. Surprisingly, the disruptions do not cause lethality during embryogenesis, with many individual mutants surviving to late stages of puparium formation. Therefore, the experiments proposed here will not only permit the analysis of how embryonic genes interact to form more refined expression patterns, but also how these patterns control cell fate decisions important for the formation of the larval and adult body form. *** ; Oh +' 0 $ H l D h R:\WWUSER\TEMPLATE\NORMAL.DOT S u m m a r y I n f o r m a t i o n ( 9513550 eozsaruh eozsaruh @ @ @ @ @ @ F # Microsoft Word 6.0 2 ; e = e a a j j j j j j j 4 1 e T + 4 j 4 j j j j ~ j j j j . 9513550 Small A central question in modern biology is how