POSITIONAL INFORMATION REGULATION DURING LEG DEVELOPMENT THROUGH FGF AND WNT SIGNALING

通过 FGF 和 WNT 信号调节腿部发育过程中的位置信息

• 批准号: 10480190
• 负责人: SAIGO Kaoru
• 金额: $ 8.06万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10480190/
• 关键词: Drosophila; Wnt; Wingless; FGF; Frizzled; Bar; Aristaless; Lim1; WNT; モルフォゲン; 位置情報; 肢形成; モルファゲン; チロシンキナーゼ; Yan

Vertebrate limbs and invertebrate appendages are formed through subdivision of the corresponding developing field, whose formation is governed by concentration garadients of various morphogen signals such as Wnt and FGF.Each subdomain, possibly with its own particular properties such as specificity in local cell adhesivity, may be specificed by a combinatorial region-specific expression of transcription factors. We isolated and characterized some new genes encoding morphogen receptors and transcriptional factors involved in the development of Drosophila legs and other organs. Here, we describe only the properties of the following two genes because of the limitation of space.We first identified Dfrizzled-3 as a gene encoding the third member of the Drosophila Frizzled family. In contrast to frizzled and frizzled-2, the Dfrizzled-3 gene was transcriptionally upregulated by Wingless signaling. Although Dfrizzled-3 protein was capable of binding to Wingless in vitro, Wingless-dependent Arm … More adillo/beta-catenin stabilization occurred much less effectively on Drosophila cells transfected with Dfrizzled-3 than those with Dfrizzled-2. Flies lacking Dfrizzled-3 activity were viable and fertile, with few morphological defects. Genetic and immunological analysis indicated that the absence of Dfrizzled-3 activity suppresses the effects of hypomorphic wingless mutations such as failure of wing and antenna formation and restores target gene expression to the normal levels without change in wingless expression. Wingless signaling may thus be attenuated by Dfrizzled-3 at least in wingless hypomorphic mutants.During Drosophila leg development, the distal-most compartment (pretarsus) and its immediate meighbour (tarsal segment 5) are specificied by a pretarsus-specific homeobox gene, aristaless, and tarsal-segment-specific Bar homeoboxes, respectively ; the pretarsus/tarsal segment boundary is formed by antagonistic interactions between Bar and pretarsus-specific genes that include aristaless. In this connection, we identified Drosophila Lim-1, a homologue of vertebrate Lim1 encoding a LIM-homeodomain protein, is involved in pretarsus specification and boundary formation through its activation of aristaless. Ectopic expression of Lim1 caused aristaless misexpression, while aristaless was significantly reduced in Lim1-null mutant clones. Pretarsus Lim1 expression was negatively regulated by Bar and abolished in leg discs lacking aristaless activity, which was associated with strong Bar misexpression in the presumptive pretarsus. No Lim1 misexpression occurred upon aristaless misexpression. The concerted function of Lim1 and aristaless was required to maintain Fasciclin 2 expression in border cells and form a smooth pretarsus/tarsal segment boundary. Lim1 was also required for femur, coxa and antennal development. Less

脊椎动物的四肢和无脊椎动物的附肢是通过相应发育区域的细分而形成的，其形成受各种形态发生信号（如Wnt和FGF）的浓度梯度控制。每个亚结构域可能具有其自身的特殊性质，如局部细胞粘附性的特异性，可能由转录因子的组合区域特异性表达来特异性地表达。我们分离并鉴定了一些新的基因编码的形态受体和转录因子参与果蝇的腿和其他器官的发展。由于篇幅所限，本文仅对以下两个基因的特性进行描述：首先确定Dfrizzled-3是果蝇Frizzled家族的第三个成员基因。与frizzled和frizzled-2相反，Dfrizzled-3基因通过Wingless信号传导在转录上上调。虽然Dfrizzled-3蛋白能够在体外与Wingless结合，但Wingless依赖性臂 ...更多信息 与用Dfrizzled-2转染的果蝇细胞相比，用Dfrizzled-3转染的果蝇细胞中adillo/β-连环蛋白稳定化的效果要差得多。缺乏Dfrizzled-3活性的苍蝇是可行的和肥沃的，几乎没有形态缺陷。遗传学和免疫学分析表明，Dfrizzled-3活性的缺乏抑制了半形态无翅突变的影响，如翅膀和天线形成的失败，并将靶基因表达恢复到正常水平而不改变无翅表达。因此，Dfrizzled-3至少在无翅亚型突变体中可以减弱无翅信号传导。（pretarsus）和它的直接的巨大的（跗节5）分别由前跗节特异性同源框基因、无芒同源框和跗节特异性Bar同源框特异性;前跗骨/跗骨节段边界由Bar和包括无芒的前跗骨特异性基因之间的拮抗相互作用形成。在这方面，我们确定了果蝇Lim-1，脊椎动物Lim1的同源物编码的LIM同源结构域蛋白，参与前跗骨规范和边界的形成，通过其激活aristaless。Lim1的异位表达引起aristaless错误表达，而aristaless在Lim1无效突变克隆中显著降低。Pretarsus Lim1表达负调控酒吧和废除腿盘缺乏aristaless活动，这是与强大的酒吧在推定pretarsus的错误表达。无aristaless错误表达时，没有Lim1错误表达。Lim1和aristaless的协调功能需要维持Fasciclin 2在边缘细胞中的表达，并形成平滑的前跗骨/跗骨段边界。Lim1也是股骨、髋和触角发育所必需的。少

项目成果

Hideki Koike: "1.8A crystal structure of the major NAD(P)H:FMN oxidoreductase of a bioluminescent bacterium, Vibrio fisdcheri" J.Mol.Biol.280. 185-315 (1998)

Hideki Koike：“生物发光细菌 Fisdcheri 弧菌的主要 NAD(P)H:FMN 氧化还原酶的 1.8A 晶体结构”J.Mol.Biol.280。

Takashi Hayashi: "Specification of promary pigment cell and outer photoreceptor fates by BarH1 homeobox gene in the developing Drosophila eye."Dev.Biol.. 200. 131-145 (1998)

Takashi Hayashi：“果蝇眼睛发育过程中 BarH1 同源盒基因对原代色素细胞和外部光感受器命运的规范。”Dev.Biol.. 200. 131-145 (1998)

Makoto Sato, Tetsuya Kojima, Tatsuo Michiue and Kaoru saigo: "Bar homeobox genes are latitudinal prepattern genes in the developing Drosophila notum whose expression is regulated by the concerted functions of decapentaplegic and wingless."Development. 126

Makoto Sato、Tetsuya Kojima、Tatsuo Michiue 和 Kaoru Saigo：“Bar 同源盒基因是发育中的果蝇 notum 中的纬度预模式基因，其表达受到十肢麻痹和无翅的协同功能的调节。”发育。

Tetsuya Kojima: "Formation and specification of distal leg segments in Drosphila by dual Bar homeobox genes,BarH1 and BarH2"Development. 127. 769-778 (2000)

Tetsuya Kojima：“通过双 Bar 同源盒基因 BarH1 和 BarH2 在果蝇中形成和规范远端腿节”开发。

Takuya Tsuji, Atsushi Sato, Ichiro Hiratani, Nasanori Taira, Kaoru Saigo and Tetsuya Kojima: "Requirement of Lim1, a Drosophaila LIM-homeobox gene, for normal leg and antennal development."Development. 127. 4315-4323 (2000)

Takuy​​a Tsuji、Atsushi Sato、Ichiro Hiratani、Nasanori Taira、Kaoru Saigo 和 Tetsuya Kojima：“正常腿部和触角发育所需的果蝇 LIM 同源盒基因 Lim1。”开发。