Developmental System Drift in Nematode Gut Specification

在胚胎发育过程中，基因网络使细胞沿着沿着分化途径发育。这种网络的变化是在进化过程中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主要表型变化的情况下发生变化，这种现象称为发育系统漂移（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。在DSD的更令人惊讶的例子中，有一些涉及转录因子网络的重新布线，其中一个新的网络取代了祖先的网络。本属的线虫是一个远亲的研究物种C。优雅该项目将使用生物信息学和遗传学方法相结合，以了解祖先Pristionchus物种中的简单胚胎基因网络如何随着进化时间的推移而扩展，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年里，合子加塔转录因子网络已经阐明，该网络指定了C.线虫胚胎在该网络中，因子按MED-1、2 END-1、3 ELT-2、7的顺序起作用，其中ELT-2作为主要的末端肠分化因子。MED/END/ELT-7因子仅见于C.优雅我们最近报道，在更远的亲戚C。angaria，gut由仅由ELT-3 ELT-2组成的更简单的网络指定。In C.在线虫中，ELT-3的肠道特化作用已被MED/END/ELT-7因子所取代。我们已经发现证据表明，更远的亲戚太平洋棱纹瓢虫（Pristionchus pacificus）指定内胚层具有扩展的加塔因子网络作为C。优雅像小杆线虫一样，这个网络似乎也来自一个更简单的祖先版本，早期的状态由Pristionchus属的现存物种代表。所有的上游因子似乎都来自祖先ELT-3样因子。在这个建议中，我们将确定的肠道规格网络的架构在Pristionchus物种，以确定网络进化的模式，并作为一个比较，小杆线虫。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的新见解。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.