| Summary: | 碩士 === 國立臺灣大學 === 動物學系 === 86 === Hedgehog (Hh) 蛋白質是一種分泌性的傳訊分子，在脊椎或無脊椎動
物的發 育及體制形成上扮演著極為重要的角色。果蠅
(Drosophila melanogaster) 的hh突變體會導致胚胎腹部體節
的方向極性受損，形成所謂的「節向性 狀」(segment
polarity phenotype)，而已知的節向基因多為Wingless (Wg) 或
Hh信息傳遞系統的成員。本論文報導了一個新的果蠅基因taroid (tr) 的
遺傳分 析以及其發育功能的探討。此新基因乃篩選自221株以EMS
引致突變的致死突 變株，透過種細胞遺傳重組技術 (the
FLP-DFS technique)分析發現，缺少tr基因 的母源成分的tr突變胚
胎呈現出所謂的lawn-of-denticles節向性狀。在tr突變胚 胎中，
分別偵測Wg信息的標的engrailed (en)與Hh信息的標的wg在表皮細胞
的蛋白質表現，得知Wg的分解消失比En來的早，顯示Hh信息傳遞需要在tr
的功能正常時才能進行。
進一步分析tr對過量表現的Wg和Hh的遺傳上位關係 (epistatic
relationship)， Wg異位表現的效應在 tr突變胚胎中不會被抑制，反之
Hh異位表現則會被tr 突變所抑制，顯示tr的確作用在Hh下游
而非Wg下游。然而，tr突變不會影響 Hh信息的標的基因
decapentaplegic在imaginal discs上的表現，只會使眼睛分化 過
程中morphogenetic furrow的推進略微延遲，因此我們推測可能有重複的
信息 路徑與tr的路徑平行存在，能補償缺少tr的效應。
未來，我們將繼續分析tr與其他Hh傳訊成員的遺傳上位關係，同時進行tr
基因 的分子選殖，以確切了解其作用機制。本研究除了希望能探索
Hh信息傳遞路徑 的未知領域，也期盼能在若干因Hh信息失調而
導致的發育不正常及癌症發生的 研究中做出貢獻。
The hedgehog (hh) gene family encode intercellular signaling
molecules that play key roles in the pattern formation of
both vertebrate and invertebrate animals. In Drosophila
melanogaster, mutation of hh gene disrupts the polarity within
each segment in the abdomen of embryo and is thereby
belonged to "the segment polarity mutation". Most
of this class of mutations have been identified to play
roles in either Wingless (Wg) or Hh signaling pathways.
This thesis reports the recovery of a novel segment polarity
gene, taroid (tr). Withthe efficient FLP-DFS technique, the
tr1094 allele was recovered from 221 EMS- induced zygotic
lethal mutations. The homozygous mutant embryos derived from
tr1094 germline clones exhibited the so-called "lawn-of-
denticles" segment polarity phenotype. Analyzing the
expression of Wg and Hh target genes, Engrailed (En) and
Wg, respectively, in epidermal cells of tr mutant embryos, the
decay of Wg protein is earlier and more severely than
that of En protein. It suggests it is more likely the
requirement of tr in Hh signaling that targeted Wg expression.
The epistatic interaction of tr mutant to overexpressed Wg and
Hh consistently suggests that tr acts downstream of Hh but
not of Wg. The effect of ectopically expressed Wg can be
seen in tr null embryos while that of ectopically expressed
Hh cannot. However, hh-dependent Dpp expression on imaginal
discs is not affected in cells lacking tr function
while the morphogenetic furrow progression of eye discs in
these tr mutant cells is slightly retarded. The existence of
parallel pathways that may compensate the tr function is thus
hypothesized. Further investigation will
focus on the verification of the epistatic relationship between
tr and other known components in the Hh signaling and the
molecular characterization of products encoded by the
tr gene. The study of tr is intended not only to increase our
realization of Hh signaling pathway but also to improve our
knowledge in the mechanism of certain developmental disorders
and human cancers that were recently indicated to
be caused by the disruption of Hh signaling.
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