Development of the mammalian telencephalon, which is the most complex region of the central nervous system, is precisely orchestrated by many signaling molecules. Wnt signaling derived from the cortical hem, a signaling center, is crucial for telencephalic development including cortical patterning and the induction of hippocampal development. Secreted protein R-spondin (Rspo) 1–4 and their receptors, leucine-rich repeat-containing G-protein-coupled receptor (Lgr) 4–6, act as activators of Wnt signaling. Although Rspo expression in the hem during the early stages of cortical development has been reported, comparative expression analysis of Rspos and Lgr4–6 has not been performed. In this study, we examined the detailed spatiotemporal expression patterns of Rspo1–4 and Lgr4–6 in the embryonic and postnatal telencephalon to elucidate their functions. In the embryonic day (E) 10.5–14.5 telencephalon, Rspo1–3 were prominently expressed in the cortical hem. Among their receptors, Lgr4 was observed in the ventral telencephalon, and Lgr6 was highly expressed throughout the telencephalon at the same stages. This suggests that Rspo1–3 and Lgr4 initially regulate telencephalic development in restricted regions, whereas Lgr6 functions broadly. From the late embryonic stage, the expression areas of Rspo1–3 and Lgr4–6 dramatically expanded; their expression was found in the neocortex and limbic system, such as the hippocampus, amygdala, and striatum. Increased Rspo and Lgr expression from the late embryonic stages suggests broad roles of Rspo signaling in telencephalic development. Furthermore, the Lgr⁺ regions were located far from the Rspo⁺ regions, especially in the E10.5–14.5 ventral telencephalon, suggesting that Lgrs act via a Rspo-independent pathway.

哺乳动物端脑是中枢神经系统最复杂的区域，其发育是由许多信号分子精确协调的。源自皮质下缘（信号中心）的 Wnt 信号对于端脑发育（包括皮质模式和海马发育的诱导）至关重要。分泌蛋白 R-spondin (Rspo) 1-4 及其受体、富含亮氨酸重复序列的 G 蛋白偶联受体 (Lgr) 4-6，充当 Wnt 信号传导的激活剂。尽管已经报道了皮层发育早期阶段下摆中 Rspo 的表达，但尚未进行 Rspos 和 Lgr4-6 的比较表达分析。在本研究中，我们检查了胚胎和出生后端脑中Rspo1-4和Lgr4-6的详细时空表达模式，以阐明它们的功能。在胚胎日 (E) 10.5–14.5 端脑，Rspo1 – 3在皮质下摆显着表达。在它们的受体中，Lgr4在腹侧端脑中观察到，而Lgr6在同一阶段在整个端脑中高表达。这表明Rspo1-3和Lgr4最初调节受限区域的端脑发育，而Lgr6 的功能广泛。从胚胎晚期开始，Rspo1-3和Lgr4-6的表达区域急剧扩大；它们的表达存在于新皮质和边缘系统，例如海马体、杏仁核和纹状体。胚胎后期Rspo和Lgr表达增加表明 Rspo 信号在端脑发育中发挥广泛作用。此外，Lgr ⁺区域远离Rspo ⁺区域，特别是在 E10.5–14.5 腹侧端脑，表明 Lgrs 通过不依赖于 Rspo 的途径发挥作用。