Wen Zilong, Wu Jinzhi, Yao Jiawen, Fang Fugui, Ju Siyu, Wang Chenxu, Liu Xingyong, Wang Deshou
Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, Southwest University, Chongqing 400715, China.
Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing 400715, China.
Cells. 2025 Aug 6;14(15):1213. doi: 10.3390/cells14151213.
The evolutionary loss of in specific vertebrate lineages, such as mammals and cypriniform fish, raises fundamental questions about its functional necessity and potential redundancy or synergy with paralogous endothelin receptors in pigment cell development. In teleosts possessing both and (e.g., Nile tilapia), their respective and combined roles in regulating neural crest-derived pigment cell precursors remains unresolved. Using CRISPR/Cas9, we generated single and double mutants to dissect their functions. We demonstrated that and synergistically govern the differentiation and migration of iridophore precursors. While is broadly essential for iridophore development, plays a unique and indispensable role in the colonization of iridophores in the dorsal iris. Double mutants exhibit near-complete iridophore loss; severe depletion of melanophores, xanthophores, and erythrophores; and a striking, fertile, transparent phenotype. Crucially, this iridophore deficiency does not impair systemic guanine synthesis pathways. mRNA rescue experiments confirmed as a key downstream effector within the Ednrb signaling cascade. This work resolves the synergistic regulation of pigment cell fates by Ednrb receptors and establishes a mechanism for generating transparent ermplasm.
在特定脊椎动物谱系中，如哺乳动物和鲤形目鱼类，其进化上的缺失引发了关于其功能必要性以及在色素细胞发育中与旁系内皮素受体潜在冗余或协同作用的基本问题。在同时拥有 和 的硬骨鱼（如尼罗罗非鱼）中，它们在调节神经嵴衍生的色素细胞前体方面各自及联合发挥的作用仍未得到解决。我们使用CRISPR/Cas9技术构建了单突变体和双突变体以剖析它们的功能。我们证明 和 协同控制虹彩细胞前体的分化和迁移。虽然 对虹彩细胞发育广泛至关重要，但 在背侧虹膜中虹彩细胞的定植方面发挥着独特且不可或缺的作用。双突变体表现出几乎完全的虹彩细胞缺失；黑素细胞、黄色素细胞和红细胞严重减少；以及一种显著的、可育的透明表型。至关重要的是，这种虹彩细胞缺陷并不损害全身鸟嘌呤合成途径。mRNA拯救实验证实 是Ednrb信号级联反应中的关键下游效应器。这项工作解决了Ednrb受体对色素细胞命运的协同调节问题，并建立了一种产生透明种质的机制。
