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内容記述 |
Almost all animals develop from a single cell, fertilized egg, with multiple and progressive processes. In these processes, that we call DEVELOPMENT, fertilized egg is divided, proliferates, and differentiates into specific tissues or organs to form precise adult body. A major challenge in developmental biology is the elucidation of how a pattern is formed.<br /> One general mode of pattern formation of the living things is based on the "Morphogen" and "Positional information", which is well known as French flag model. Another general mode of pattern formation is "Prepattern" proposed by Stern in 1968 based on his work of bristle patterning of Drosophila. The prepattern concept is based on that in order to make a pattern it is necessary to generate a spatial variation in something which resembles in some way the pattern. This mode of pattern formation is useful for explain a precise and complex pattern formation for instance a bristle pattern of adult Drosophila.<br /> On the dorsal part of the mesothorax (called notum) of Drosophila, large bristles (macrochaetes) develop in fixed numbers at constant positions. Pattern formation of macrochaetes on the notum has provided an ideal model system for studying two-dimensional patterning. The accurate positioning of the macrochaetes is established during the third larval to early pupal stage within the epithelial sheets of the notum region of the wing imaginal discs (thoracic disc). Initially, in the thoracic disc, a group of cells called a proneural cluster, characterized by the expression of the proneural genes achaete (ac) and scute (sc), are formed around the positions where macrochaetes will form. Namely, precise positioning of the macrochaete on the notum depends on the complex expression pattern of the ac and sc genes in the thoracic disc.<br /> Hence the factors that establish a prepattern on the notum must affect the expression of proneural genes. Recently, several genes which contribute to the establishment of prepattern (we call these genes "prepattern genes") on the notum were characterized. For instance, pannier (pnr) which encodes a GATA family transcription factor, extramacrochaetae (emc) which encodes a helix-loop-helix protein devoid of a basic domain, were identified as prepattern genes. These genes are expressed some specific regions of the thoracic disc, and seem to establish a prepattern on the notum field.<br /> Local specific expression of prepattern genes could explain the pattern formation of macrochaetes on the notum. However, one of the problems of prepatterning on the notum (indeed this is a problem of prepattern concept itself) is how local maxima (or minima) of prepattern gene expression (or activation/repression of the prepattern gene product) are generated. One possible explanation about this problem is that some morphogen gradients could contribute the regulation of prepattern genes expression on the notum, suggesting that two general approaches of pattern formation are inseparable and parts of same developmental process.<br /> One candidate factor that can contributes to the establishment of prepattern on the notum as a morphogen gradient is Decapentaplegic (Dpp). Dpp is a BMP family member protein that is thought to play essential roles in the development of various species. Dpp is thought to acts as a morphogen, and provides the positional information to cells in the wing imaginal disc. This property suggests that Dpp could participate in the prepattern formation in the thoracic disc.<br /> In this study, he has attempted to reveal how morphogen gradient contributes to the establishment of prepattern, using the notum region of Drosophila as a model system. In chapter 2, whether Dpp, as a morphogen gradient, plays a part in the prepatterning of the macrochaetes on the notum were examined. Experiments using both gain-of-function and conditional loss-of-function mutants for Dpp signaling revealed that Dpp participates in this process in two major ways. One is induction of the proneural cluster in cooperation with signaling of Wingless (Wg), which is a Wnt family member protein, and the other is restriction of the wg expression domain in the thoracic disc. Furthermore, the analysis using different copies of activated Dpp receptor expressing flies suggesting that a difference should exist between the threshold level of Dpp signaling required for proneural gene induction and that required for repression of wg expression. In chapter 3, first, the expressions of two prepattern genes, pnr and u-shaped (ush) on the loss-of and gain-of-function mutants for Dpp signaling were examined. These analyses revealed that both pnr and ush expression is positively regulated by Dpp signaling in a concentration dependent manner. Then, the mechanisms for the regulation of notal wg expression were analyzed. Analysis of wg expression in wild-type and several allelic combinations of pnr mutants revealed that Pnr has two opposing roles, induction and repression, in the regulation of the wg expression, and that Ush switches the activator function to the repressor. It is also shown that notal wg expression is affected by Wg signaling itself. In the last chapter, the presented results and combined mechanism of pattern formation were summarized.<br /> These findings suggest that the pattern formation based on morphogen is not an antithesis of prepattern, but rather these two modes of pattern formation are parts of same developmental process in the patterning of the Drosophila developing notum. |
要旨・審査要旨 / Abstract, Screening Result (283.1 kB)
