Developmental System Drift in Nematode Gut Specification

线虫肠道规格中的发育系统漂移

• 批准号: 2341162
• 负责人: Morris Maduro
• 金额: $ 129万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-01-15 至 2027-12-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2341162&HistoricalAwards=false
• 关键词: Developmental; System; Drift; Nematode; Gut

During embryonic development, gene networks cause cells to develop along pathways of differentiation. Changes in such networks underlie differences in form and function that emerge over evolutionary time. However, gene networks can also undergo changes without any major phenotype change, a phenomenon called Developmental System Drift (DSD). DSD is inferred when a common developmental process is found to have differences in the underlying gene networks between two species, even though the phenotype is the same. Among the more surprising examples of DSD are those involving the rewiring of a transcription factor network, where a new network replaces an ancestral one. Nematodes of the genus Pristionchus are a distant relative of the well-studied species C. elegans. This project will use a combination of bioinformatic and genetics methods to understand how a simple embryonic gene network in ancestral Pristionchus species underwent expansion over evolutionary time to form a more complex network. The project will also provide teaching and training opportunities for graduate and undergraduate students, including through a freshman laboratory course in nematode genetics, bioinformatics, microscopy, and molecular biology.Over the past 20 years, network of zygotic GATA transcription factors has been elucidated that specifies the gut precursor in the C. elegans embryo. In this network, factors act in the order MED-1,2 END-1,3 ELT-2,7, with ELT-2 acting as the main terminal intestinal differentiation factor. The MED/END/ELT-7 factors are found only in close relatives of C. elegans. We recently reported that in the more distant relative C. angaria, gut is specified by a simpler network consisting of only ELT-3 ELT-2. In C. elegans, the gut specification role of ELT-3 has been replaced by the MED/END/ELT-7 factors. We have found evidence that the more distant relative Pristionchus pacificus specifies endoderm with an expanded GATA factor network as C. elegans. Like Caenorhabditis, this network seems to also be derived from a simpler ancestral version, with earlier states represented by extant species in the Pristionchus genus. All upstream factors appear to be derived from an ancestral ELT-3-like factor. In this proposal, we will determine the architecture of the gut specification network in Pristionchus species to identify patterns of network evolution, and as a comparison to Caenorhabditis. The proposed studies promise new insights into embryonic development of Pristionchus nematodes, the evolution of gene networks, and Developmental System Drift.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在胚胎发育过程中，基因网络使细胞沿着分化的路径发展。这种网络的变化是随着进化时间的推移而出现的形式和功能差异的基础。然而，基因网络也可以在没有任何重大表型变化的情况下发生变化，这种现象被称为发育系统漂移(DSD)。当发现一个共同的发育过程在两个物种之间的潜在基因网络中存在差异时，即使表型相同，也可以推断出DSD。其中更令人惊讶的DSD的例子是涉及转录因子网络的重新连接，即一个新的网络取代一个祖先的网络。Pristionchus属的线虫是研究得很好的线虫物种的远亲。该项目将结合生物信息学和遗传学方法，了解Pristionchus祖先物种的简单胚胎基因网络如何随着进化时间的推移而扩展，形成更复杂的网络。该项目还将为研究生和本科生提供教学和培训机会，包括通过一门关于线虫遗传学、生物信息学、显微镜和分子生物学的实验室课程。在过去的20年里，合子GATA转录因子网络已经被阐明，它指定线虫胚胎中的肠道前体。在这个网络中，因子的作用顺序为MED-1，2-END-1，3-ELT-2，7，ELT-2是主要的末端肠道分化因子。MED/END/ELT-7因子仅在线虫近亲中发现。我们最近报道，在更远的亲缘关系中，Gut是由一个更简单的网络指定的，该网络只由ELT-3 ELT-2组成。在线虫中，ELT-3的肠道指定作用已被MED/END/ELT-7因子所取代。我们发现有证据表明，较远的亲缘关系的Pristionchus pacephus将具有扩展的GATA因子网络的内胚层指定为线虫。像线虫一样，这个网络似乎也是从一个更简单的祖先版本衍生而来的，早期的状态由Pristionchus属的现存物种代表。所有上游因子似乎都源自一种类似于ELT-3的祖先因子。在本提案中，我们将确定Pristionchus物种的肠道规范网络的架构，以确定网络进化的模式，并作为与线虫的比较。拟议的研究承诺对Pristionchus线虫的胚胎发育、基因网络的进化和发育系统漂移有新的见解。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。