Elucidation of the molecular mechanisms that generate a remarkable open coil “banana” shell phenotype in Lymnaea stagnalis

几个世纪以来，数学家、物理学家和生物学家一直对软体动物的外壳形态进行研究。然而，产生螺旋壳的细胞和分子机制仍然未知。在这个项目中，我们将确定与壳卷曲的软体动物模型，滞水螺的遗传成分。最近发现的一个壮观的和强大的开放式螺旋“香蕉”表型产生的内分泌干扰物“度他雄胺”提供了一个理想的机会，探索控制软体动物壳卷曲的分子机制。利用转录组学方法结合原位可视化的基因表达模式，我们将能够识别和表征L。stagnalis。此外，该项目将深入了解度他雄胺在软体动物中的不一致作用机制;软体动物不具有结合双氢睾酮所需的核受体（度他雄胺靶向5α-还原酶，产生双氢睾酮的酶），因此在软体动物中观察到对度他雄胺的如此强烈反应的方式和原因仍不清楚。虽然L.虽然滞水软体动物是经合组织正式承认的生物哨兵物种，但由于缺乏关于其在软体动物中的作用方式的知识，其在环境中检测内分泌活性化学品的全部潜力受到阻碍。因此，该项目也将大大有助于欧洲和泛北极水道的环境监测。

Molluscan shell morphologies have been admired and studied by mathematicians, physicists and biologists for centuries. However, the cellular and molecular mechanisms that generate a coiled shell remain unknown. In this project we will identify the genetic components associated with shell coiling in a mollusc model, Lymnaea stagnalis. The recent discovery of a spectacular and robust open coil “banana” phenotype generated in response to the endocrine disruptor ‘dutasteride’ presents an ideal opportunity to explore the molecular mechanisms that control molluscan shell coiling. Using a transcriptomics approach coupled with in situ visualization of gene expression patterns, we will be able to identify and characterize the major genetic components of the shell-coiling program in L. stagnalis. In addition, this project will provide insight into the incongruous mechanism of action of dutasteride in molluscs; molluscs do not possess the nuclear receptors required to bind dihydrotestosterone (dutasteride targets 5α-reductase, the enzyme that produces dihydrotestosterone), therefore how and why such a robust response to dutasteride is observed in molluscs remains obscure. Although L. stagnalis is a formally recognised OECD bio-sentinel species, its full potential to detect endocrine-active chemicals in the environment is hampered by a lack of knowledge regarding their modes of action in molluscs. Therefore, this project will also significantly contribute to the environmental monitoring of European and holarctic waterways.