Collaborative Research: Developmental Mechanisms Underlying Diversity in Arthropod Limbs

合作研究：节肢动物四肢多样性的发育机制

• 批准号: 9874624
• 负责人: Lisa Nagy
• 金额: $ 21万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-15 至 2002-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9874624&HistoricalAwards=false
• 关键词: Collaborative; Research; Developmental; Mechanisms; Underlying

One important feature that has enabled arthropods to become the most diverse extant animals is the adaptability of their limb morphology. Evolutionary modifications have resulted in limbs that differ radically in form and function, from unbranched walking legs to multibranched swimming paddles. Drs. Nagy and Williams' goal is determine the developmental and genetic mechanisms that underlie the formation of branched versus unbranched limbs in order to understand how arthropod limb diversity has evolved. Their preliminary experiments allow them to formulate an initial model for how a multi-branched limb develops in the crustacean, Triops longicaudatus. This model predicts which features of the current Drosophila model of limb development are modified in the evolution of other arthropod limbs. They propose comparative gene expression studies, fate mapping, and descriptions of the cellular dynamics of limb growth to confirm or extend our model of Triops limb development. They then will experimentally test our model by observing the consequences of targeted cell ablations in developing limbs. Through comparisons with Drosophila, they hope to explain how radically different limb morphologies can be produced by modifications of similar underlying genetic networks. Their studies compare both the molecular and cellular development of a multi-branched limb in Triops to that of the unbranched limb in Drosophila. These two limbs differ not only in number of branches but also in their fundamental structure: Drosophila legs are jointed and rod-shaped, Triops legs have an unjointed paddle-shaped limb with eight branches arising around the margin. Thus, their comparison between them should reveal how very different limbs arise. Their results suggest that there are three critical features of the Drosophila model that vary between species. 1) In Drosophila, the intersection of the anteroposterior (A/P) and dorsoventral (D/V) patterning axes position the limb primordia. Their data suggest that variation in D/V positioning in Triops results in the specification of a larger limb primordia, which they hypothesize is the first step in building a multi-branched limb. 2) In Drosophila, the intersection of the secreted signaling factors, wingless (wg), decapentaplegic (dpp), and hedgehog (hh) specify a point of proximal/ distal (P/D) elongation for leg outgrowth. Cell fates in the distal region of the leg are activated and maintained directly by different levels of Wg and Dpp signals; in the proximal region of the leg they are activated by a different gene network, regulated at least in part by the extradenticle (exd) gene. Their data suggest that the multibranched limb of Triops does indeed have a single P/D axis, potentially controlled by homologues of the same signaling genes. However, the patterning of the branches in Triops is not a simple iteration of the same gene network involved in patterning the Drosophila limb. From their earliest development at least four different branch types are identifiable by distinctive gene expression patterns. 3) Establishment of a single point of P/D outgrowth in Drosophila is not directly linked to cell division patterns. However, in Triops, they find a concentration of mitotically active cells in the region of the putative Triops limb organizer. Their model therefore suggests that, unlike Drosophila, the P/D organizer in Triops may control specific patterns of cell division, in a manner similar to vertebrate limb development.

使节肢动物成为最多样化的现存动物的一个重要特征是它们的肢体形态的适应性。进化的修改导致了肢体在形式和功能上的根本不同，从无分支的行走腿到多分支的游泳桨。 纳吉和威廉姆斯博士的目标是确定分支与非分支肢体形成的发育和遗传机制，以了解节肢动物肢体多样性是如何进化的。 他们的初步实验使他们能够制定一个初始模型，以了解甲壳类动物Triops longicaudatus的多分支肢体是如何发育的。 该模型预测了当前果蝇肢体发育模型的哪些特征在其他节肢动物肢体的进化中被修改。他们提出了比较基因表达研究，命运映射和肢体生长的细胞动力学描述，以确认或扩展我们的Triops肢体发育模型。然后，他们将通过观察发育肢体中靶向细胞消融的后果来实验性地测试我们的模型。 通过与果蝇的比较，他们希望解释如何通过修改类似的潜在遗传网络来产生完全不同的肢体形态。他们的研究比较了Triops中多分支肢体的分子和细胞发育与果蝇中无分支肢体的分子和细胞发育。 这两种肢不仅在分支的数量上不同，而且在它们的基本结构上也不同：果蝇的腿是有关节的杆状，Triops的腿有一个无关节的桨状肢，边缘有八个分支。 因此，它们之间的比较应该揭示出非常不同的肢体是如何产生的。他们的研究结果表明，果蝇模型的三个关键特征在物种之间存在差异。1)在果蝇中，前后（A/P）和背腹（D/V）模式轴的交叉点定位肢体原基。 他们的数据表明，Triops中D/V定位的变化导致了更大的肢体原基的特化，他们假设这是构建多分支肢体的第一步。 2)在果蝇中，分泌的信号因子wingless（wg）、decapentaplegic（dpp）和hedgehog（hh）的交叉点指定了腿长出的近端/远端（P/D）伸长点。 腿远端区域的细胞命运直接由不同水平的Wg和Dpp信号激活和维持;在腿的近端区域，它们由不同的基因网络激活，至少部分由外齿（exd）基因调控。他们的数据表明，Triops的多分支肢体确实有一个单一的P/D轴，可能由相同信号基因的同源物控制。 然而，Triops中分支的模式化并不是果蝇肢体模式化所涉及的相同基因网络的简单迭代。 从它们最早的发育开始，至少有四种不同的分支类型可以通过独特的基因表达模式来识别。 3)在果蝇中建立单点P/D生长与细胞分裂模式没有直接联系。 然而，在Triops中，他们在假定的Triops肢体组织者区域发现了有丝分裂活性细胞的集中。 因此，他们的模型表明，与果蝇不同，Triops中的P/D组织者可能以类似于脊椎动物肢体发育的方式控制细胞分裂的特定模式。