Cellular retinoic acid binding proteins regulate germ cell proliferation and sex determination in zebrafish.

IF 3.7 2区生物学 Q1 DEVELOPMENTAL BIOLOGY

Development Pub Date : 2024-11-22 DOI:10.1242/dev.202549

Lianna Fung, Daniel B Dranow, Arul Subramanian, Natalia Libby, Thomas F Schilling

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引用次数: 0

Abstract

Cellular retinoic acid (RA) binding proteins (Crabps) solubilize intracellular RA and transport it to its nuclear receptors or cytoplasmic degradation enzymes. Despite their extreme conservation across chordates, genetic studies of Crabp function have revealed few essential functions. We have generated loss-of-function mutations in all four zebrafish Crabps and find essential roles for Crabp2s in gonad development and sex determination. Transgenic RA reporters show strong RA-responses in germ cells at the bipotential stage of gonad development. Double mutants lacking the functions of both Crabp2a and Crabp2b predominantly become male, which correlates with their smaller gonad size and reduced germ cell proliferation during gonad development at late larval and early juvenile stages. In contrast, mutants lacking the functions of both Crabp1a and Crabp1b have normal sex ratios. Exogenous RA treatments at bipotential gonad stages increase germ cell number, consistent with a direct role for RA in promoting germ cell proliferation. Our results suggest essential functions for Crabps in gonad development and sex determination.

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细胞视黄酸结合蛋白调控斑马鱼生殖细胞增殖和性别决定

细胞视黄酸（RA）结合蛋白（Crabps）可溶解细胞内的 RA，并将其转运至核受体或细胞质降解酶。尽管 Crabp 在脊索动物中极为罕见，但对其功能的遗传研究却很少发现其基本功能。我们在所有四种斑马鱼 Crabps 中都产生了功能缺失突变，并发现 Crabp2s 在性腺发育和性别决定中的重要作用。在性腺发育的双潜能期，转基因 RA 报告者在生殖细胞中显示出强烈的 RA 反应。缺乏 Crabp2a 和 Crabp2b 功能的双突变体主要为雄性，这与其在幼虫后期和幼虫早期性腺发育过程中性腺体积较小、生殖细胞增殖减少有关。相反，缺乏 Crabp1a 和 Crabp1b 功能的突变体性别比例正常。在性腺双潜能期外源 RA 处理可增加生殖细胞数量，这与 RA 在促进生殖细胞增殖方面的直接作用一致。我们的研究结果表明，Crabps在性腺发育和性别决定中具有重要功能。

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来源期刊

Development 生物-发育生物学

CiteScore

6.70

自引率

4.30%

发文量

433

审稿时长

3 months

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