Hairy and Enhancer of Split 6 (Hes6) Deficiency in Mouse Impairs Neuroblast Differentiation in Dentate Gyrus Without Affecting Cell Proliferation and Integration into Mature Neurons

Abstract

Hes6 is a member of the hairy-enhancer of split homolog (Hes) family of transcription factors and interacts with other Hes family genes. During development, Hes genes are expressed in neural stem cells and progenitor cells. However, the role of Hes6 in adult hippocampal neurogenesis remains unclear. We therefore investigated the effects of Hes6 on adult hippocampal neurogenesis, by comparing Hes6 knockout and wild-type mice. To this end, we immunostained for markers of neural stem cells and progenitor cells (nestin), proliferating cells (Ki67), post-mitotic neuroblasts and immature neurons (doublecortin, DCX), mature neuronal cells (NeuN), and astrocyte (S100β). We also injected 5-bromo-2'-deoxyuridine (BrdU) to trace the fate of mitotic cells. Nestin- and Ki67-positive proliferating cells did now show any significant differences between wild and knockout groups. Hes6 knockout negatively affects neuroblast differentiation based on DCX immunohistochemistry. On the contrary, the ratio of the BrdU and NeuN double-positive cells did not show any significance, even though it was slightly higher in the knockout group. These results suggest that Hes6 is involved in the regulation of neuroblast differentiation during adult neurogenesis, but does not influence integration into mature neurons.

Ascorbic Acid Mitigates D-galactose-Induced Brain Aging by Increasing Hippocampal Neurogenesis and Improving Memory Function

“…At 12 weeks of age, the animals ( n = 10 in each group) received an intraperitoneal injection of 5-bromo-2′-deoxyuridine (BrdU; Sigma, St. Louis, MO, USA) at a dosage of 50 mg/kg in saline twice daily for three consecutive days to examine the effects of D-gal and ascorbic acid treatment on the differentiation of BrdU-positive cells into mature neurons in the dentate gyrus [21]. Animals were sacrificed four weeks after the final day of BrdU treatment for histology analysis (Figure 1).…”

“…Double immunofluorescence staining was performed as described in the previous study [21]. DNA denaturation was conducted for BrdU immunostaining.…”

Overexpression of HES6 has prognostic value and promotes metastasis via the Wnt/β-catenin signaling pathway in colorectal cancer

“…The oncogenic role of HES6, a helix-loop-helix transcriptional suppressor, has been previously reported in several studies: for example, HES6 was demonstrated to regulate the differentiation of numerous cell types during myogenesis ( 27 ). Nam et al ( 28 ) proposed that HES6 binds to HES1, suppressing the function of HES1 and promoting the differentiation of neural stem cells. Additionally, elevated HES6 expression was reported to lead to a significant increase in the invasive phenotype of prostate cancer and glioma ( 14 , 29 ).…”

Long Noncoding RNA (lncRNA) MIR22HG Suppresses Gastric Cancer Progression through Attenuating NOTCH2 Signaling

“…Results from this research suggested that silencing MIR22HG might enhance gastric cancer cells proliferation, migration and invasion by increasing HES6, HEY1 and nucleus NOTCH2 expression. HES6, a member of the hairy-enhancer of the split homolog family, was found to be involved in multiple tumors [25]. It was reported that elevated HES6 expression of patients with hepatocellular carcinoma exhibited adverse prognosis [26].…”