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

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.

Activation of lipophagy ameliorates cadmium-induced neural tube defects via reducing low density lipoprotein cholesterol levels in mouse placentas

“…Worldwide, 1 in every 1000 pregnancies has a NTD and they cause enormous clinical, economic, and societal costs (Fimia et al 2007 ; Zhang et al 2016 ). Since China implemented a nationwide folic acid supplementation program in 2009, the prevalence of NTDs has dropped from 7.8% to 3.1% in five years (Chen et al 2021a ). Although many studies have confirmed that strengthening folic acid intake during perinatal pregnancy can reduce the incidence and recurrence rate of NTDs, not all types of NTDs can be prevented, so in-depth research into the causes of the disease is important to advance its diagnosis, treatment and research (Cao et al 2024 ).…”

A replication study on key neurodevelopmental pathways affected by valproate treatment of neural precursor cells

“…Another study by Zhang et al, 2017 also shows an increase in p-Akt in rat primary cortical neurons post-valproate treatment (Table 2). All of the above pathways are also reported to play an important role in neural tube closure defects (Rolo et al, 2018; Bekri et al, 2019; Han et al, 2020; Chen et al, 2021; Li et al, 2021; Tian et al, 2022).…”

A quest for genetic causes underlying signaling pathways associated with neural tube defects

“…Experimental studies on mouse models have shown that overexpression of retinoic acid leads to neural tube defects ( 236 , 237 ). A recent study found that treatment of neural crest cells (NSCs) with all-trans-retinoic acid culminates in neural tube deformities ( 238 ). Notch signaling pathway: The notch signaling pathway regulates the proliferation and differentiation of NSCs (neural crest cells) during embryonic development.…”

“…Previous Studies observed that mutation in the genes Hes1, Hes3, and RBP-Jκ of the Notch signaling pathway contributes to neural tube anomalies ( 121 , 149 ). A recent study observed that abnormal expression of N1 (Notch1) enforces the occurrence of neural tube deformities ( 238 ). A study conducted on embryonic stem cells showed that the double mutant embryo of CSL (CBF-1/Suppressor of hairless/Lag-1) displays the phenotypes of neural tube defects ( 241 ).…”

“…Experimental studies on mouse models have shown that overexpression of retinoic acid leads to neural tube defects ( 236 , 237 ). A recent study found that treatment of neural crest cells (NSCs) with all-trans-retinoic acid culminates in neural tube deformities ( 238 ).…”