Regulation of neural differentiation by the transcription factor HES and the receptor Notch in mammals

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13670011
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: KYOTO UNIVERSITY
• Principal Investigator: ISHIBASHI Makoto Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (30232341)
• Co-Investigator(Kenkyū-buntansha): SHIOTA Kohei Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (80109529)
• Project Period (FY): 2001 – 2002
• Keywords: Neural differentiation / transcriptions factor / HES / Notch signaling

Research Abstract

Helix-loop-helix type transcription factor, HES, inhibits neural differentiation in mice. HES has to be properly regulated as neural differentiation proceeds. Genetic analysis in Drosophila suggested that expression of Hes gene is under control of Notch signaling. To elucidate molecular mechanisms of this regulation, we examined the regulatory elements of Hes gene. The data showed that Hes expression is upregulated by Notch signaling through RBP-Jk/Su(H) binding sites.
Although Notch signaling itself had been known to repress neural differentiation, it remained to be an open question whether Hes gene is downstream to Notch signaling. To demonstrate this cascade in mouse neural differentiation, neural precursor cells and the retina from Hes1/5 knockout embryos were infected with Notch-transducing retrovirus. While neural differentiation was inhibited by a Notch signal in wild type, Hes1 knockouts and Hes5 knockouts, neural precursors of Hes1 and Hes5 compound mutants normally differentiated in presence of a Notch signal. The data suggest that Hes1 and Hes5 are necessary for inhibition of neural differentiation by Notch, and that Hes1 and Hes5 are functionally redundant.