Murine Delta Homologue, mDelta1, Expressed on Feeder Cells Controls Cellular Differentiation

Cell Structure and Function

Yoshiro Wada¹  Makoto Yazaki¹  Tadashi Matsubayashi²  Keigo Mizutani²  Takahiro S. Doi²  Yuichi Obata²  Shigeru Iwase²  Toshitada Takahashi²  Kenji Kasai² 

[1] Department of Pediatrics, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuhoku, Nagoya 467-8601, and;Laboratory of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusaku, Nagoya, 464-8681,

关键词: Delta;    Serrate-Notch pathway;    mDelta1;    intercellular signaling;    inhibition of differentiation;    inductive signal;   

DOI  :  10.1247/csf.25.21

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(58)Cited-By(4)The Delta/Serrate-Notch pathway is involved in intercellular signaling that controls cell fate during the development of invertebrates and vertebrates. Delta is a prototype of Notch ligands and has been studied extensively in Drosophila. In higher vertebrates, four Delta/Serrate homologues and four Notch homologues have been identified. Recent studies showed that the murine Delta homologue, mDelta1, is essential in early embryogenesis. The biological activity of mammalian Delta and its roles in cellular differentiation, however, have remained unclear. In this study, we first surveyed expression of mDelta1 in the adult mouse and found it to be present in a wide range of tissues. For testing biological activity of mDelta1, we expressed a mDelta1 full-length cDNA in L cells using a eukaryotic expression vector. Effects of mDelta1 on cellular differentiation were examined in two independent systems, featuring C2C12 myogenic differentiation and multipotent murine bone marrow cell differentiation. Inhibition of the former was observed with mDelta1 expression on L cells, associated with suppression of myogenin, a myogenic transcription factor. Expression of mDelta1 in conjunction with GM-CSF promoted differentiation of bone marrow cells to myeloid dendritic cells at the expense of other lineages. Although the effects of mDelta1 on two differentiation systems appeared opposing, as inhibition occurring in one and induction in the other, this can be understood by the unifying concept of generation of diverse cell types from equivalent progenitors. Thus, the present study provided evidence that mammalian Delta participates in intercellular signaling, determining the cell fate in a wide variety of tissues.

【 授权许可】

Unknown