背景:大脑的性分化发生在所有主要脊椎动物谱系中,但在分子和细胞水平上尚未得到很好的理解。不像大多数脊椎动物,变性鱼在成年期对社会刺激具有显著的改变生殖性的能力,提供了一个独特的机会来理解神经系统可以启动和协调性分化的机制。
方法:本研究使用单核RNA测序技术在海葵鱼两栖鱼中探索前脑的性别分化,产生第一个改变性别的大脑的细胞图谱。
结果:我们发现了细胞类型特异性基因表达的广泛性别差异,细胞的相对比例,基线神经元兴奋,并预测了神经元间的交流。此外,我们确定了胆囊收缩素,甘丙肽,和雌激素系统作为性分化的中心分子轴。在这些发现的支持下,我们提出了一个在保守的脊椎动物社会决策网络中的性别分化模型,该网络跨越神经元和神经胶质的多个亚型,包括位于视前区域内的神经元亚群,以调节性腺分化。
结论:这项工作加深了我们对脊椎动物大脑中性别分化的理解,并定义了一套丰富的分子和细胞途径,这些途径在海葵鱼的成年性别变化过程中进行分化。
这项研究为性别变化的海葵鱼(Amphiprionocellaris)的大脑性别差异提供了关键见解,一种在成年后根据社会环境改变性别的物种。使用单核RNA测序,该研究提供了第一个脑细胞图谱,显示了两个关键生殖区域的性别差异:视前区和端脑。该研究确定了细胞类型比例和基因表达的显着性别差异,特别是在共表达神经肽胆囊收缩素的放射状神经胶质和谷氨酸能神经元中。它还突出了可能参与性腺调节的视前区神经元的差异。这项工作加深了我们对脊椎动物大脑性别分化的理解,尤其是那些能够改变成人性别的人,并阐明该过程的关键分子和细胞起点和终点。
BACKGROUND: Sexual differentiation of the brain occurs in all major vertebrate lineages but is not well understood at a molecular and cellular level. Unlike most vertebrates, sex-changing fishes have the remarkable ability to change reproductive sex during adulthood in response to social stimuli, offering a unique opportunity to understand mechanisms by which the nervous system can initiate and coordinate sexual differentiation.
METHODS: This study explores sexual differentiation of the forebrain using single nucleus RNA-sequencing in the anemonefish Amphiprion ocellaris, producing the first cellular atlas of a sex-changing brain.
RESULTS: We uncover extensive sex differences in cell type-specific gene expression, relative proportions of cells, baseline neuronal excitation, and predicted inter-neuronal communication. Additionally, we identify the cholecystokinin, galanin, and estrogen systems as central molecular axes of sexual differentiation. Supported by these findings, we propose a model of sexual differentiation in the conserved vertebrate social decision-making network spanning multiple subtypes of neurons and glia, including neuronal subpopulations within the preoptic area that are positioned to regulate gonadal differentiation.
CONCLUSIONS: This work deepens our understanding of sexual differentiation in the vertebrate brain and defines a rich suite of molecular and cellular pathways that differentiate during adult sex change in anemonefish.
This study provides key insights into brain sex differences in sex-changing anemonefish (Amphiprion ocellaris), a species that changes sex in adulthood in response to the social environment. Using single nucleus RNA-sequencing, the study provides the first brain cellular atlas showing sex differences in two crucial reproductive areas: the preoptic area and
telencephalon. The research identifies notable sex-differences in cell-type proportions and gene expression, particularly in radial glia and glutamatergic neurons that co-express the neuropeptide cholecystokinin. It also highlights differences in preoptic area neurons likely involved in gonadal regulation. This work deepens our understanding of sexual differentiation of the brain in vertebrates, especially those capable of adult sex change, and illuminates key molecular and cellular beginning and endpoints of the process.