Breaking through the bottleneck: Krogh's principle in behavioral neuroendocrinology and the potential of gene editing.
Breaking through the bottleneck: Krogh's principle in behavioral neuroendocrinology and the potential of gene editing.
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DOI：
10.1093/icb/icad068
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发表时间：
2023-06
影响因子：
2.6
通讯作者：
Lillian R. Jackson;Mariana S. Lopez;Beau A. Alward
中科院分区：
文献类型：
--
作者：
Lillian R. Jackson;Mariana S. Lopez;Beau A. Alward
1929年，奥古斯特·克罗写道，对于生物学中的每一个问题，都有一个物种或物种集合，在这个物种或物种集合中，追求这样的问题最适合获得最深刻的见解。这句话被称为“克罗原理”，是许多生物学家的指导性力量。在实践中，克罗的原理可能会指导对双亲照料感兴趣的生物学家选择不使用实验室小鼠，而是研究存在双亲照料且明显可观察到的物种，例如某些毒蛙物种。在实验室小鼠中，雌性承担了大部分育儿任务。这种解决生物学问题的方法是卓有成效的，新技术可以实现更深入的见解。然而，直到最近，对于对某些基因的功能感兴趣的生物学家来说，Krogh原理的一个重要局限性是，某些技术仅适用于少数传统模式生物，如小鼠、果蝇、斑马鱼和线虫，其中测试分子系统在生物过程中的功能可以使用基因敲除(KO)和转基因技术。这些方法通常比非传统模式生物中常用的其他方法(例如药理学)更精确，以解决类似的问题。因此，对我们理解这些机制的分子控制的一些最深入的见解来自于少数遗传上易驯化的物种。基因编辑技术的最新进展，如CRISPR(集群规则散布短回文重复)/Cas9基因编辑作为实验室工具，改变了生物学家应用克罗原理所能获得的洞察力。从这个角度来看，我们将利用在一种受欢迎的社会行为模式物种--非洲罗非鱼Astatotilapia burtoni中的发现，来强调Krogh原理的令人兴奋的潜力。具体地说，我们将重点介绍从20世纪70年代现场观察中获得的关于伯顿沙门氏菌中性类固醇激素(雄激素和雌激素)控制社会地位的研究中获得的见解，以及最近在实验室研究中从CRISPR/Cas9基因编辑中获得的新见解。我们的评论强调了在A.burtoni中的发现，可能会为其他使用Krogh原理的人提供一个路线图，目的是将基因编辑纳入他们的研究计划。因此，基因编辑是一种强大的免费实验室工具，研究人员可以用它来产生新的见解，以了解非传统模式生物的生理和行为的分子机制。
In 1929, August Krogh wrote that for every question in biology, there is a species or collection of species in which pursuing such questions is the most appropriate for achieving the deepest insights. Referred to as "Krogh's Principle", these words are a guiding force for many biologists. In practice, Krogh's principle might work to guide a biologist interested in studying bi-parental care to choose not to use lab mice, in which the female does most of the parenting, but instead study species in which bi-parental care is present and clearly observable, such as in certain poison frog species. This approach to pursuing biological questions has been fruitful, with more in-depth insights achievable with new technologies. However, up until recently, an important limitation of Krogh's principle for biologists interested in the functions of certain genes, was certain techniques were only available for a few traditional model organisms such as mice, fruit flies, zebrafish, and C. elegans, in which testing the functions of molecular systems on biological processes can be achieved using genetic knockout (KO) and transgenic technology. These methods are typically more precise than other approaches (e.g., pharmacology) commonly used in non-traditional model organisms to address similar questions. Therefore, some of the most in-depth insights into our understanding of the molecular control of these mechanisms have come from a small number of genetically tractable species. Recent advances in gene editing technology such as CRISPR (Clustered Regularly Interspersed Short Palindromic Repeats)/Cas9 gene editing as a laboratory tool has changed the insights achievable for biologists applying Krogh's principle. In this perspective, we will highlight the exciting potential of Krogh's principle using discoveries made in a popular model species of social behavior, the African cichlid fish Astatotilapia burtoni. Specifically, we will focus on insights gained from studies of the control of social status by sex steroid hormones (androgens and estrogens) in A. burtoni that originated during field observations during the 1970s, and have recently culminated in novel insights from CRISPR/Cas9 gene editing in laboratory studies. Our review highlighting discoveries in A. burtoni may function as a roadmap for others using Krogh's principle aiming to incorporate gene editing into their research program. Gene editing is thus a powerful complimentary laboratory tool researchers can use to yield novel insights into understanding the molecular mechanisms of physiology and behavior in non-traditional model organisms.