背景:已经彻底研究了胚胎脑脊液(eCSF)在大脑发育初期的重要作用。这种液体含有适当的大脑发育的关键分子,如Wnt和FGF家族的成员,载脂蛋白,和视黄醇结合蛋白。然而,这些分子的来源仍然不确定,因为它们存在于脉络丛形成之前,通常被称为脑脊液的主要生产者。连合下器官(SCO)是位于间脑中的高度保守的腺体,是最早的分化脑结构之一。SCO将分子分泌到eCSF中,在脉络丛分化之前,在这种流体的稳态和动力学中起着关键作用。SCO分泌的关键分子之一是SCO-spondin,与维持正常心室大小有关的蛋白质,脊柱直轴,神经发生,和轴突引导。此外,SCO分泌转甲状腺素蛋白和碱性成纤维细胞生长因子2,而eCSF中的其他鉴定分子可能由SCO分泌。此外,在上海合作组织中已经鉴定出各种转录因子。然而,上海合作组织早期发展所涉及的确切机制尚未完全理解。
结果:为了揭示与SCO在大脑发育过程中的作用有关的关键分子参与者和信号通路,我们进行了转录组学分析,比较了HH23和HH30阶段(分别为4天和7天)的雏鸡SCO。此外,来自HH30整个小鸡脑的公开转录组数据用于比较SCO和全脑转录组之间的表达水平。这些分析表明,在这两个阶段,SCO差异表达骨形态发生蛋白的几个成员,Wnt和成纤维细胞生长因子家族,涉及轴突导向的多种蛋白质,神经源性和分化分子,细胞受体和转录因子。分泌途径在HH30阶段特别上调,而增殖途径在HH23阶段增加。
结论:结果表明,SCO具有在其他结构发育之前向eCSF分泌几种形态发生分子的能力,比如脉络丛.
BACKGROUND: The significant role of embryonic cerebrospinal fluid (eCSF) in the initial stages of brain development has been thoroughly studied. This fluid contains crucial molecules for proper brain development such as members of the Wnt and FGF families, apolipoproteins, and retinol binding protein. Nevertheless, the source of these molecules remains uncertain since they are present before the formation of the choroid plexus, which is conventionally known as the primary producer of cerebrospinal fluid. The subcommissural organ (SCO) is a highly conserved gland located in the
diencephalon and is one of the earliest differentiating brain structures. The SCO secretes molecules into the eCSF, prior to the differentiation of the choroid plexus, playing a pivotal role in the homeostasis and dynamics of this fluid. One of the key molecules secreted by the SCO is SCO-spondin, a protein involved in maintenance of the normal ventricle size, straight spinal axis, neurogenesis, and axonal guidance. Furthermore, SCO secretes transthyretin and basic fibroblast growth factor 2, while other identified molecules in the eCSF could potentially be secreted by the SCO. Additionally, various transcription factors have been identified in the SCO. However, the precise mechanisms involved in the early SCO development are not fully understood.
RESULTS: To uncover key molecular players and signaling pathways involved in the role of the SCO during brain development, we conducted a transcriptomic analysis comparing the embryonic chick SCO at HH23 and HH30 stages (4 and 7 days respectively). Additionally, a public transcriptomic data from HH30 entire chick brain was used to compare expression levels between SCO and whole brain transcriptome. These analyses revealed that, at both stages, the SCO differentially expresses several members of bone morphogenic proteins, Wnt and fibroblast growth factors families, diverse proteins involved in axonal guidance, neurogenic and differentiative molecules, cell receptors and transcription factors. The secretory pathway is particularly upregulated at stage HH30 while the proliferative pathway is increased at stage HH23.
CONCLUSIONS: The results suggest that the SCO has the capacity to secrete several morphogenic molecules to the eCSF prior to the development of other structures, such as the choroid plexus.