Leerberg Dena M, Sano Kaori, Draper Bruce W
Department of Molecular and Cellular Biology, University of California, Davis, California, United States of America.
Graduate school of Science and Technologies, Sophia University, Tokyo, Tokyo, Japan.
PLoS Genet. 2017 Sep 5;13(9):e1006993. doi: 10.1371/journal.pgen.1006993. eCollection 2017 Sep.
The vertebrate ovary and testis develop from a sexually indifferent gonad. During early development of the organism, primordial germ cells (the gamete lineage) and somatic gonad cells coalesce and begin to undergo growth and morphogenesis to form this bipotential gonad. Although this aspect of development is requisite for a fertile adult, little is known about the genetic regulation of early gonadogenesis in any vertebrate. Here, we provide evidence that fibroblast growth factor (Fgf) signaling is required for the early growth phase of a vertebrate bipotential gonad. Based on mutational analysis in zebrafish, we show that the Fgf ligand 24 (Fgf24) is required for proliferation, differentiation, and morphogenesis of the early somatic gonad, and as a result, most fgf24 mutants are sterile as adults. Additionally, we describe the ultrastructural elements of the early zebrafish gonad and show that distinct somatic cell populations can be identified soon after the gonad forms. Specifically, we show that fgf24 is expressed in an epithelial population of early somatic gonad cells that surrounds an inner population of mesenchymal somatic gonad cells that are in direct contact with the germ cells, and that fgf24 is required for stratification of the somatic tissue. Furthermore, based on gene expression analysis, we find that differentiation of the inner mesenchymal somatic gonad cells into functional cell types in the larval and early juvenile-stage gonad is dependent on Fgf24 signaling. Finally, we argue that the role of Fgf24 in zebrafish is functionally analogous to the role of tetrapod FGF9 in early gonad development.
脊椎动物的卵巢和睾丸由未分化的性腺发育而来。在生物体的早期发育过程中,原始生殖细胞(配子谱系)和体细胞性腺细胞结合并开始生长和形态发生,形成这种具有双向潜能的性腺。尽管性腺发育的这一方面对于成年后的生育能力是必需的,但在任何脊椎动物中,早期性腺发生的遗传调控却知之甚少。在这里,我们提供证据表明成纤维细胞生长因子(Fgf)信号传导是脊椎动物双向潜能性腺早期生长阶段所必需的。基于斑马鱼的突变分析,我们表明Fgf配体24(Fgf24)是早期体细胞性腺增殖、分化和形态发生所必需的,因此,大多数Fgf24突变体成年后不育。此外,我们描述了早期斑马鱼性腺的超微结构元件,并表明性腺形成后不久就能识别出不同的体细胞群体。具体而言,我们表明Fgf24在早期体细胞性腺细胞的上皮群体中表达,该上皮群体围绕着与生殖细胞直接接触的间充质体细胞性腺细胞的内部群体,并且Fgf24是体细胞组织分层所必需的。此外,基于基因表达分析,我们发现幼虫和幼年早期性腺中内部间充质体细胞性腺细胞向功能细胞类型的分化依赖于Fgf24信号传导。最后,我们认为Fgf24在斑马鱼中的作用在功能上类似于四足动物FGF9在早期性腺发育中的作用。