Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411, Tartu, Estonia.
Institute of Molecular and Cell Biology, University of Tartu, Vanemuise 46-221, Ria 23-204, 51010, Tartu, Estonia.
Sci Rep. 2024 Sep 30;14(1):22593. doi: 10.1038/s41598-024-73358-z.
Deletions and malfunctions of the IgLON family of cell adhesion molecules are associated with anatomical, behavioral, and metabolic manifestations of neuropsychiatric disorders. We have previously shown that IgLON genes are expressed in sensory nuclei/pathways and that IgLON proteins modulate sensory processing. Here, we examined the expression of IgLON alternative promoter-specific isoforms during embryonic development and studied the sensory consequences of the anatomical changes when one of the IgLON genes, Negr1, is knocked out. At the embryonal age of E12.5 and E13.5, various IgLONs were distributed differentially and dynamically in the developing sensory areas within the central and peripheral nervous system, as well as in limbs and mammary glands. Sensory tests showed that Negr1 deficiency causes differences in vestibular function and temperature sensitivity in the knockout mice. Sex-specific differences were noted across olfaction, vestibular functioning, temperature regulation, and mechanical sensitivity. Our findings highlight the involvement of IgLON molecules during sensory circuit formation and suggest Negr1's critical role in somatosensory processing.
IgLON 家族细胞黏附分子的缺失和功能障碍与神经精神疾病的解剖、行为和代谢表现有关。我们之前已经表明,IgLON 基因在感觉核/通路中表达,并且 IgLON 蛋白调节感觉处理。在这里,我们在胚胎发育过程中检查了 IgLON 替代启动子特异性异构体的表达,并研究了当 IgLON 基因之一 Negr1 被敲除时解剖变化的感觉后果。在胚胎年龄 E12.5 和 E13.5,各种 IgLON 在中枢和周围神经系统以及四肢和乳腺中发育中的感觉区域中以不同的方式动态分布。感觉测试表明,Negr1 缺乏导致敲除小鼠在前庭功能和温度敏感性方面存在差异。嗅觉、前庭功能、温度调节和机械敏感性方面存在性别特异性差异。我们的研究结果强调了 IgLON 分子在感觉回路形成过程中的参与,并表明 Negr1 在躯体感觉处理中起着关键作用。