Fut9 Deficiency Causes Abnormal Neural Development in the Mouse Cerebral Cortex and Retina

被引:5
作者
Abdullah, Asmaa [1 ]
Hayashi, Yoshitaka [1 ]
Morimura, Naoko [1 ]
Kumar, Akhilesh [2 ]
Ikenaka, Kazuhiro [2 ]
Togayachi, Akira [3 ]
Narimatsu, Hisashi [3 ]
Hitoshi, Seiji [1 ,2 ]
机构
[1] Shiga Univ Med Sci, Dept Integrat Physiol, Otsu, Shiga 5202192, Japan
[2] Grad Univ Adv Studies, Sch Life Sci, Dept Physiol Sci, Okazaki, Aichi 4448787, Japan
[3] Natl Inst Adv Ind Sci & Technol, Res Ctr Med Glycosci, Glycogene Funct Team, Tsukuba, Ibaraki 3058568, Japan
关键词
Fucosyltransferase; Neural stem cells; Retinal precursor cells; Migration; Corticothalamic projection neurons; ALPHA-1,3-FUCOSYL-TRANSFERASE-IX FUT9; STEM-CELLS; DIFFERENTIATION; SCHIZOPHRENIA; DISAPPEARANCE; EXPRESSION; PRECURSOR; PROTEIN;
D O I
10.1007/s11064-022-03651-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2793 / 2804
页数:12
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