Effect of Notch1 on neural tube defects and neural stem cell differentiation induced by all‑<em>trans</em> retinoic acid

Chen,Na; Xu,Jiaming; Zhang,Xinying; Li,Shuwei; Zhu,Weiwei; Cui,Haibin; Sun,Yu; Han,Bo; Ma,Aihua

doi:10.3892/mmr.2021.11859

Effect of Notch1 on neural tube defects and neural stem cell differentiation induced by all‑trans retinoic acid

Authors:
- Na Chen
- Jiaming Xu
- Xinying Zhang
- Shuwei Li
- Weiwei Zhu
- Haibin Cui
- Yu Sun
- Bo Han
- Aihua Ma
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Affiliations: Department of Pediatrics, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China, Department of Pediatrics, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
Published online on: January 21, 2021 https://doi.org/10.3892/mmr.2021.11859
Article Number: 220

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Abstract

Neural tube defects (NTDs) are the most serious and common birth defects in the clinical setting. The Notch signaling pathway has been implicated in different processes of the embryonic neural stem cells (NSCs) during neural tube development. The aim of the present study was to investigate the expression pattern and function of Notch1 (N1) in all‑trans retinoic acid (atRA)‑induced NTDs and NSC differentiation. A mouse model of brain abnormality was established by administering 28 mg/kg atRA, and then brain development was examined using hematoxylin and eosin (H&E) staining. The N1 expression pattern was detected in the brain of mice embryos via immunohistochemistry and western blotting. NSCs were extracted from the fetal brain of C57 BL/6 embryos at 18.5 days of pregnancy. N1, Nestin, neurofilament (NF), glial fibrillary acidic protein (GFAP) and galactocerebroside (GALC) were identified using immunohistochemistry. Moreover, N1, presenilin 1 (PS1), Nestin, NF, GFAP and GALC were detected via western blotting at different time points in the NSCs with control media or atRA media. H&E staining identified that the embryonic brain treated with atRA was more developed compared with the control group. N1 was downregulated in the embryonic mouse brain between days 11 and 17 in the atRA‑treated group compared with the untreated group. The distribution of N1, Nestin, NF, GFAP and GALC was positively detected using immunofluorescence staining. Western blotting results demonstrated that there were significantly, synchronous decreased expression levels of N1 and PS1, but increased expression levels of NF, GFAP and GALC in NSCs treated with atRA compared with those observed in the controls (P<0.05). The results suggested that the N1 signaling pathway inhibited brain development and NSC differentiation. Collectively, it was found that atRA promoted mouse embryo brain development and the differentiation of NSCs by inhibiting the N1 pathway.

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