Sspo, also known as SCO-spondin, is a gene encoding a large monomeric protein. The protein SCO-spondin forms Reissner's fiber (RF) in the cerebrospinal fluid (CSF), which plays a role in CSF circulation in mammalian models. In zebrafish, RF and CSF-contacting neurons form an axial sensory system related to spine morphogenesis [2,3,5].

Genetic models have provided insights into Sspo's function. Sspo knockout mice lack RF-positive material in the subcommissural organ (SCO) and fibrillar condensates in brain ventricles. These mice exhibit reduced brain ventricle sizes and minor thoracic spine curvature defects, indicating that SSPO and RF regulate ventricle size during development and moderately impact spine geometry [2,3]. In zebrafish, sspo mutants develop severe vertebral column curvatures resembling human idiopathic scoliosis, with reduced expression of urotensin related peptide genes in CSF-contacting neurons, and treatment with catecholamine or Urp2 can rescue the axial defects [5]. In addition, multi-omics examination in a study on neoadjuvant therapy for gastric cancer revealed SSPO mutation as a putative biomarker for pathological responses [1]. In a mouse model of primary aldosteronism, Sspo mutation was associated with higher aldosterone values, increased aldosterone-to-renin ratio, and adrenal Cyp11b2 overexpression [4].

In conclusion, Sspo is crucial for the development and function related to the central nervous system, especially in aspects of brain ventricle size regulation, spine morphogenesis, and may also be involved in disease-related biomarker discovery and physiological regulation of aldosterone. The Sspo knockout mouse models and zebrafish mutants have significantly contributed to understanding its functions in these areas, and its potential role in gastric cancer biomarker discovery and primary aldosteronism pathophysiology is also notable.

References:

1. Li, Song, Yu, Wenbin, Xie, Fei, Sheng, Lei, Liu, Lian. 2023. Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer. In Nature communications, 14, 8. doi:10.1038/s41467-022-35431-x. https://pubmed.ncbi.nlm.nih.gov/36596787/

2. Xu, Huixin, Dugué, Guillaume P, Cantaut-Belarif, Yasmine, Wyart, Claire, Lehtinen, Maria K. 2023. SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation. In Fluids and barriers of the CNS, 20, 89. doi:10.1186/s12987-023-00491-8. https://pubmed.ncbi.nlm.nih.gov/38049798/

3. Xu, Huixin, Dugué, Guillaume P, Cantaut-Belarif, Yasmine, Wyart, Claire, Lehtinen, Maria K. 2023. SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.08.01.551512. https://pubmed.ncbi.nlm.nih.gov/37577601/

4. Perez-Rivas, L G, Rhayem, Y, Sabrautzki, S, Beuschlein, F, Spyroglou, A. 2016. Genetic characterization of a mouse line with primary aldosteronism. In Journal of molecular endocrinology, 58, 67-78. doi:10.1530/JME-16-0200. https://pubmed.ncbi.nlm.nih.gov/27965370/

5. Lu, Hao, Shagirova, Aidana, Goggi, Julian L, Yeo, Hui Li, Roy, Sudipto. 2020. Reissner fibre-induced urotensin signalling from cerebrospinal fluid-contacting neurons prevents scoliosis of the vertebrate spine. In Biology open, 9, . doi:10.1242/bio.052027. https://pubmed.ncbi.nlm.nih.gov/32409296/