van der Weele Corine M, Hospes Katrina C, Rowe Katherine E, Jeffery William R
bioRxiv. 2024 Jun 9:2024.06.09.598120. doi: 10.1101/2024.06.09.598120.
The teleost consists of surface dwelling (surface fish) and cave dwelling (cavefish) forms. Cavefish have evolved in subterranean habitats characterized by reduced oxygen levels (hypoxia) and show constructive and regressive phenotypic traits controlled by increased Sonic hedgehog (Shh) signaling along the embryonic midline. The enhancement of primitive hematopoietic domains, which are formed bilaterally in the anterior and posterior lateral plate mesoderm, are responsible for the development of more larval erythrocytes in cavefish relative to surface fish. In this study, we determine the role of hypoxia and Shh signaling in the development and evolution of primitive hematopoiesis in cavefish. We show that hypoxia treatment during embryogenesis increases primitive hematopoiesis and erythrocyte development in surface fish. We also demonstrate that upregulation of Shh midline signaling by treatment with the Smoothened agonist SAG increases primitive hematopoiesis and erythrocyte development in surface fish, whereas Shh downregulation via treatment with the Smoothened inhibitor cyclopamine decreases these traits in cavefish. Together these results suggest that hematopoietic enhancement is regulated by hypoxia and the Shh signaling system. Lastly, we demonstrate that hypoxia treatment enhances expression of Shh signaling along the midline of surface fish embryos. Thus, we conclude that a hypoxia-Shh axis may drive the adaptive evolution of primitive hematopoiesis and erythrocyte development in cavefish.
Hypoxia increases hematopoiesis and erythrocytes in surface fishShh upregulation increases hematopoiesis and erythrocytes in surface fishShh inhibition decreases hematopoiesis and erythrocytes in cavefishHypoxia upregulates Shh along the embryonic midline in surface fish.
硬骨鱼包括表层栖息（表层鱼类）和洞穴栖息（洞穴鱼）两种形态。洞穴鱼在以低氧水平（缺氧）为特征的地下栖息地中进化，表现出由沿胚胎中线增加的音猬因子（Shh）信号控制的建设性和退行性表型特征。原始造血区域在前侧和后侧板中胚层两侧形成，其增强导致洞穴鱼相对于表层鱼产生更多的幼体红细胞。在本研究中，我们确定了缺氧和Shh信号在洞穴鱼原始造血发育和进化中的作用。我们发现胚胎期缺氧处理可增加表层鱼的原始造血和红细胞发育。我们还证明，用 smoothened 激动剂 SAG 处理上调 Shh 中线信号可增加表层鱼的原始造血和红细胞发育，而用 smoothened 抑制剂环杷明处理下调 Shh 则会降低洞穴鱼的这些特征。这些结果共同表明，造血增强受缺氧和 Shh 信号系统调节。最后，我们证明缺氧处理可增强表层鱼胚胎中线处 Shh 信号的表达。因此，我们得出结论，缺氧-Shh 轴可能驱动洞穴鱼原始造血和红细胞发育的适应性进化。
缺氧增加表层鱼的造血和红细胞数量
Shh上调增加表层鱼的造血和红细胞数量
Shh抑制降低洞穴鱼的造血和红细胞数量
缺氧上调表层鱼胚胎中线处的Shh 。
