title: Interaction of Hand2 and E2a is important for transcription of Phox2b in sympathetic nervous system neuron differentiation.
abstract: Transcription factors play a crucial role in the development of various tissues. In particular, the transcription factors of the basic helix-loop-helix (bHLH) family are crucial regulators of neurodifferentiation. Previous studies suggested that the bHLH transcription factor Hand2 is essential for sympathetic nervous system neuron differentiation in vivo, but the molecular mechanisms involved have not been well elucidated. It is important for understanding their mode of action in cellular differentiation to clarify how these bHLH factors regulate distinct transcriptional targets in a temporally and spatially controlled manner. Recent reports on ES cell differentiation suggested that its molecular mechanism mimics that of in vivo neurogenesis. However, the diverse nature of ES cell populations has prevented efficient analysis. To address this issue, we previously established a cell line in P19 embryonal carcinoma (EC) cells. Efficient sympathetic nervous system (SNS) neuron differentiation is induced in the cell line. Using this cell line, we succeeded in showing that the interaction of bHLH transcription factor Hand2 with E2a is required for transcription of Phox2b, which is essential for autonomic nervous system neuron development, and this binding activates this expression in SNS differentiation. Moreover, we also demonstrated that Hes5 regulated the transcription of Phox2b as a negative regulator and it inhibited the SNS differentiation. These findings have enabled us to determine the novel regulatory mechanism of Phox2b in SNS differentiation.
authors: Faculty of Industrial Science and Technology, Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
authors: Yusuke
authors: Y
authors: Hashimoto
authors: Mikaho
authors: M
authors: Tsutsumi
authors: Reiko
authors: R
authors: Myojin
authors: Keiko
authors: K
authors: Maruta
authors: Fumitoshi
authors: F
authors: Onoda
authors: Fumio
authors: F
authors: Tashiro
authors: Masaya
authors: M
authors: Ohtsu
authors: Yasufumi
authors: Y
authors: Murakami
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D047468:Immunoprecipitation; D051379:Mice; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology*; D034741:RNA, Small Interfering / Q000235:genetics; D013564:Sympathetic Nervous System / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C498766:Hand2 protein, mouse; C109220:NBPhox protein; C075668:Tcf3 protein, mouse