期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 86, 期 7, 页码 1472-1481出版社
WILEY-LISS
DOI: 10.1002/jnr.21615
关键词
basic helix-loop-helix (bHLH); neuroD2; E proteins; cerebellum
资金
- NCI NIH HHS [5 R01 CA112350-02] Funding Source: Medline
- NIGMS NIH HHS [T32 GM07108, T32 GM07266] Funding Source: Medline
Loss-of-function studies have revealed the role of many basic helix-loop-helix (bHLH) transcription factors at specific points during development; however, the role of E proteins in the development of the nervous system has not been experimentally addressed. E proteins have been speculated to interact selectively with class 11 bHLH factors to form different neurogenic complexes. In this study, using coimmunoprecipitation in a culture model of neurogenesis (P19 cells), we show that E proteins E12, HEB, and E2-2 interact with neuroD2. Using electrophoretic mobility shift assay and P19 cell culture, we show that these heterodimers bind a neuroD2 preferred E box and induce neurogenesis equally well. We examine the mRNA levels of the three E proteins at 10 time points during brain development and show that E protein gene expression is regulated such that at certain times during development selective interaction between neuroD2 and a single E protein (HEB) is a possibility. This led us to study the brains of HEB and E2A knockout mice, which manifest no gross neuroanatomical, cellular, or behavioral deficits. These findings, together with homology in the primary peptide sequence of E proteins, suggest functional compensation among E proteins during development of the nervous system. (c) 2008 Wiley-Liss, Inc.
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