Department of Biology, University of Maryland, College Park, MD, 20742, USA.
Department of Biology, University of Maryland, College Park, MD, 20742, USA.
Dev Biol. 2024 Dec;516:138-147. doi: 10.1016/j.ydbio.2024.08.008. Epub 2024 Aug 21.
The teleost Astyanax mexicanus consists of surface dwelling (surface fish) and cave dwelling (cavefish) forms. Cavefish have evolved in subterranean habitats characterized by reduced oxygen levels (hypoxia) and exhibit a subset of 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 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 Shh signaling. Lastly, we demonstrate that hypoxia enhances expression of Shh signaling along the midline of surface fish embryos. We conclude that hypoxia-mediated Shh plasticity may be a driving force for the adaptive evolution of primitive hematopoiesis and erythrocyte development in cavefish.
硬骨鱼Astyanax mexicanus 由水面栖居（水面鱼）和洞穴栖居（洞穴鱼）两种形式组成。洞穴鱼是在低氧（缺氧）的地下栖息地进化而来的，表现出一系列由胚胎中线 Sonic hedgehog（Shh）信号增强控制的表型特征。原始造血区域的增强，这些区域在前侧和后侧侧板中胚层中双侧形成，是洞穴鱼相对于水面鱼具有更多幼虫红细胞发育的原因。在这项研究中，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。我们表明，胚胎发生期间的缺氧处理会增加水面鱼的原始造血和红细胞发育。我们还证明，通过 Smoothened 激动剂 SAG 上调 Shh 中线信号会增加水面鱼的原始造血和红细胞发育，而通过 Smoothened 抑制剂 cyclopamine 处理下调 Shh 会降低洞穴鱼的这些特征。这些结果表明，造血增强受缺氧和 Shh 信号的调节。最后，我们证明缺氧会增强水面鱼胚胎中线的 Shh 信号表达。我们得出结论，缺氧介导的 Shh 可塑性可能是洞穴鱼原始造血和红细胞发育适应性进化的驱动力。
