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 In C. elegans, the gut specification role of ELT-3 has been replaced by the MED/END/ELT-7 factors.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，基因网络会导致细胞沿分化途径发展。此类网络的变化是在进化时间出现的形式和功能差异的基础。但是，基因网络也可以发生变化而没有任何重大表型变化，这种现象称为发育系统漂移（DSD）。当发现共同的发展过程在两个物种之间的基本基因网络中存在差异时，即使表型相同，DSD是在基本基因网络上存在差异的。 DSD的更令人惊讶的例子包括涉及转录因子网络的重新布线的示例，其中新网络取代了祖先。 Pristionchus属的线虫是秀丽隐杆线虫的遥远亲戚。该项目将使用生物信息学和遗传学方法的组合来了解祖先pristionchus物种中的简单胚胎基因网络如何在进化时间内扩展以形成更复杂的网络。该项目还将为研究生和本科生提供教学和培训机会，包括通过线虫遗传学，生物信息学，显微镜和分子生物学的新生实验室课程。在过去的20年中，已经阐明了Zygotic GATA转录因子网络的网络，这些网络已被阐明了C. exeleans Embryo中的肠道前体。在该网络中，因子以MED-1,2 END-1,3 ELT-2,7的顺序起作用，而ELT-2充当主要的末端肠道分化因子。仅在秀丽隐杆线虫的近亲中发现了MED/END/ELT-7因子。我们最近报道说，在更遥远的相对C. angaria中，肠道由仅由ELT-3 ELT-2组成的简单网络指定。在秀丽隐杆线虫中，ELT-3的肠道规范作用已被MED/END/ELT-7因子取代。我们发现证据表明，更遥远的相对Pristionchus Pacificus将内胚层指定为延伸的GATA因子网络为秀丽隐杆线虫。像Caenorhabditis一样，该网络似乎也源自更简单的祖先版本，较早的状态在Pristionchus属中以现有物种为代表。所有上游因子似乎都来自祖先ELT-3样因子。在此提案中，我们将确定Pristionchus物种中肠道规范网络的结构，以鉴定网络进化的模式，并与Caenorhabditis进行比较。拟议的研究向Pristionchus线虫的胚胎发展，基因网络的演变和发展系统漂移提供了新的见解。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛的影响标准通过评估来进行评估的。