Fut9 Deficiency Causes Abnormal Neural Development in the Mouse Cerebral Cortex and Retina
Fut9 Deficiency Causes Abnormal Neural Development in the Mouse Cerebral Cortex and Retina
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DOI：
10.1007/s11064-022-03651-8
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发表时间：
2022-06-26
影响因子：
4.4
通讯作者：
Hitoshi, Seiji
中科院分区：
文献类型：
--
作者：
Abdullah, Asmaa;Hayashi, Yoshitaka;Hitoshi, Seiji
α 1，3-岩藻糖基转移酶9（Fut 9）负责合成刘易斯X [Le（X），Gal β 1-4（Fuc α 1-3）GlcNAc]碳水化合物表位，其是多能或多能组织特异性干细胞的标志物。虽然Fut 9缺陷小鼠表现出焦虑相关的行为，但大脑中的结构和细胞异常仍有待研究。本研究结合原位杂交和免疫组织化学技术，阐明了Fut 9和Le（X）在脑和视网膜中的时空表达。我们发现Fut 9表达细胞对Ctip 2（一种位于皮质的第V/VI层的神经元的标记物）和TLE 4（一种位于皮质的第VI层的皮质丘脑投射神经元（CThPN）的标记物）呈阳性。在胚胎第11.5天使用5-乙炔基-2MODIFIER LETTER PRIME-脱氧尿苷，在E12.5天使用5-溴-2MODIFIER LETTER PRIME-脱氧尿苷，并且在E14.5的GFP表达质粒的子宫内电穿孔揭示了在P0 Fut 9（-/-）中在E11.5在皮质的VI层/亚板中和在视网膜的神经节细胞层中产生的神经元的百分比的降低。小鼠此外，这种VI层/亚板神经元的减少持续到成年期，导致成年Fut 9（-/-）皮质V/VI层中Ctip 2（强）/Satb 2（-）兴奋性神经元数量减少。这些结果表明，Fut 9在皮层和视网膜中神经前体细胞的分化、迁移和成熟中起重要作用。
alpha 1,3-Fucosyltransferase 9 (Fut9) is responsible for the synthesis of Lewis X [Le(X), Gal beta 1-4(Fuc alpha 1-3)GlcNAc] carbohydrate epitope, a marker for pluripotent or multipotent tissue-specific stem cells. Although Fut9-deficient mice show anxiety-related behaviors, structural and cellular abnormalities in the brain remain to be investigated. In this study, using in situ hybridization and immunohistochemical techniques in combination, we clarified the spatiotemporal expression of Fut9, together with Le(X), in the brain and retina. We found that Fut9-expressing cells are positive for Ctip2, a marker of neurons residing in layer V/VI, and TLE4, a marker of corticothalamic projection neurons (CThPNs) in layer VI, of the cortex. A birthdating analysis using 5-ethynyl-2MODIFIER LETTER PRIME-deoxyuridine at embryonic day (E)11.5, 5-bromo-2MODIFIER LETTER PRIME-deoxyuridine at E12.5, and in utero electroporation of a GFP expression plasmid at E14.5 revealed a reduction in the percentage of neurons produced at E11.5 in layer VI/subplate of the cortex and in the ganglion cell layer of the retina in P0 Fut9(-/-) mice. Furthermore, this reduction in layer VI/subplate neurons persisted into adulthood, leading to a reduction in the number of Ctip2(strong)/Satb2(-) excitatory neurons in layer V/VI of the adult Fut9(-/-) cortex. These results suggest that Fut9 plays significant roles in the differentiation, migration, and maturation of neural precursor cells in the cortex and retina.