Todorović Petar, Kelam Nela, Racetin Anita, Filipović Natalija, Katsuyama Yu, Saraga-Babić Mirna, Vukojević Katarina
Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, 21000 Split, Croatia.
Department of Anatomy, Shiga University of Medical Science, Otsu 520-2192, Japan.
Genes (Basel). 2025 Aug 27;16(9):1013. doi: 10.3390/genes16091013.
: The Reelin-Dab1 signaling pathway, known for its crucial role in neurodevelopment, particularly in neuronal migration and the formation of cortical layers, has been a subject of extensive research. However, its involvement in gastrointestinal organogenesis is a relatively unexplored area. Our study investigates the expression patterns of Dab1, Reelin, PGP9.5, and Sox2 during stomach development in () mice and aims to shed light on how inactivation affects epithelial-mesenchymal signaling dynamics, thereby contributing to a deeper understanding of this pathway's non-neural functions. : Embryonic stomach tissues from and wild-type mice, collected at developmental stages E13.5 and E15.5, were examined by immunofluorescenceto evaluate the difference in expression of Dab1, Reelin, PGP9.5, and Sox2. Semi-quantitative scoring and quantitative image analysis were used to assess protein localization and intensity within epithelial and mesenchymal compartments. : Dab1 expression was significantly increased in both the epithelium and mesenchyme of mice at E13.5 and E15.5. Reelin expression in the epithelium showed a visible but statistically non-significant decrease in at E15.5, while mesenchymal expression remained low and significantly lower than controls. PGP9.5 expression was significantly reduced in epithelium at E13.5, then strongly upregulated at E15.5. Mesenchymal PGP9.5 remained consistently high. Sox2 showed no statistically significant changes but increased semi-quantitatively in epithelium and mesenchyme at E15.5. These findings highlight compartment-specific disruptions and potential compensatory mechanisms following inactivation. : Our findings indicate that deficiency leads to distinct molecular changes in epithelial and mesenchymal compartments of the developing stomach. The Reelin-Dab1 axis appears critical for epithelial-mesenchymal coordination, while PGP9.5 and Sox2 upregulation in mice may represent potential compensatory responses that could support epithelial integrity, although this remains speculative without functional validation.
瑞连蛋白-Dab1信号通路以其在神经发育，尤其是神经元迁移和皮质层形成中的关键作用而闻名，一直是广泛研究的对象。然而，其在胃肠器官发生中的作用是一个相对未被探索的领域。我们的研究调查了Dab1、瑞连蛋白、PGP9.5和Sox2在（）小鼠胃发育过程中的表达模式，旨在阐明（）基因失活如何影响上皮-间充质信号动态，从而有助于更深入地理解该通路的非神经功能。：收集E13.5和E15.5发育阶段的（）和野生型小鼠的胚胎胃组织，通过免疫荧光检查来评估Dab1、瑞连蛋白、PGP9.5和Sox2表达的差异。使用半定量评分和定量图像分析来评估上皮和间充质区室中蛋白质的定位和强度。：在E13.5和E15.5时，（）小鼠上皮和间充质中的Dab1表达均显著增加。在E15.5时，（）小鼠上皮中的瑞连蛋白表达有明显但无统计学意义的下降，而间充质表达仍然较低且显著低于对照组。在E13.5时，（）小鼠上皮中的PGP9.5表达显著降低，然后在E15.5时强烈上调。间充质中的PGP9.5一直保持高表达。Sox2无统计学显著变化，但在E15.5时，（）小鼠上皮和间充质中的Sox2半定量增加。这些发现突出了（）基因失活后的区室特异性破坏和潜在的补偿机制。：我们的研究结果表明，（）基因缺陷导致发育中的胃上皮和间充质区室发生明显的分子变化。瑞连蛋白-Dab1轴对于上皮-间充质协调似乎至关重要，而（）小鼠中PGP9.5和Sox²上调可能代表潜在的补偿反应，这可能支持上皮完整性，尽管在没有功能验证的情况下这仍然只是推测。
