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Development March 1, 2000; 127 (6): 1303-14.

Distinct effects of XBF-1 in regulating the cell cycle inhibitor p27(XIC1) and imparting a neural fate.

Hardcastle Z , Papalopulu N .

XBF-1 is an anterior neural plate-specific, winged helix transcription factor that affects neural development in a concentration-dependent manner. A high concentration of XBF-1 results in suppression of endogenous neuronal differentiation and an expansion of undifferentiated neuroectoderm. Here we investigate the mechanism by which this expansion is achieved. Our findings suggest that XBF-1 converts ectoderm to a neural fate and it does so independently of any effects on the mesoderm. In addition, we show that a high dose of XBF-1 promotes the proliferation of neuroectodermal cells while a low dose inhibits ectodermal proliferation. Thus, the neural expansion observed after high dose XBF-1 misexpression is due both to an increase in the number of ectodermal cells devoted to a neural fate and an increase in their proliferation. We show that the effect on cell proliferation is likely to be mediated by p27(XIC1), a cyclin-dependent kinase (cdk) inhibitor. We show that p27(XIC1) is expressed in a spatially restricted pattern in the embryo, including the anterior neural plate, and when misexpressed it is sufficient to block the cell cycle in vivo. We find that p27(XIC1 )is transcriptionally regulated by XBF-1 in a dose-dependent manner such that it is suppressed or ectopically induced by a high or low dose of XBF-1, respectively. However, while a low dose of XBF-1 induces ectopic p27(XIC1 )and ectopic neurons, misexpression of p27(XIC1 )does not induce ectopic neurons, suggesting that the effects of XBF-1 on cell fate and cell proliferation are distinct. Finally, we show that p27(XIC1 )is suppressed by XBF-1 in the absence of protein synthesis, suggesting that at least one component of p27(XIC1 )regulation by XBF-1 may be direct. Thus, XBF-1 is a neural-specific transcription factor that can independently affect both the cell fate choice and the proliferative status of the cells in which it is expressed.

PubMed ID: 10683182
Article link: Development

Species referenced: Xenopus
Genes referenced: acta4 actc1 actl6a cdknx elavl1 foxg1 krt12.4 neurog1 neurog2 sox3 sst.1 tubb2b znrd2

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