Developmental System Drift in Nematode Gut Specification

在胚胎发育过程中，基因网络导致细胞沿着分化途径发育。这些网络的变化是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改变的情况下发生变化，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。在DSD中更令人惊讶的例子是那些涉及转录因子网络重新布线的例子，其中一个新的网络取代了一个祖先的网络。隐杆线虫属线虫是已被充分研究的秀丽隐杆线虫的远亲。该项目将使用生物信息学和遗传学相结合的方法来了解一个简单的胚胎基因网络是如何在祖先柱头龙物种的进化过程中扩展形成一个更复杂的网络的。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等新生实验课程。在过去的20年里，已经阐明了在秀丽隐杆线虫胚胎中指定肠道前体的合子GATA转录因子网络。在这个网络中，因子的作用顺序为MED-1、2 END-1、3 ELT-2、7，其中ELT-2是主要的终端肠分化因子。MED/END/ELT-7因子仅在秀丽隐杆线虫的近亲中发现。我们最近报道，在更远的亲戚C. angaria中，肠道由仅由ELT-3和ELT-2组成的更简单的网络指定。在秀丽隐杆线虫中，ELT-3的肠道规范作用已被MED/END/ELT-7因子所取代。我们已经发现证据表明，更远的亲戚太平洋Pristionchus将具有扩展GATA因子网络的内胚层指定为秀丽隐杆线虫。与杆状线虫一样，这种网络似乎也源于一个更简单的祖先版本，早期的状态由现存的柱状线虫属物种代表。所有上游因子似乎都来源于祖先的类似elt -3的因子。在本研究中，我们将确定柱头龙物种肠道规格网络的结构，以确定网络进化模式，并与隐杆线虫进行比较。这些研究为线虫的胚胎发育、基因网络的进化和发育系统漂移提供了新的见解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.