| Budget Amount *help |
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1998: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Research Abstract |
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
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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
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