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Link to original content: https://doi.org/10.1038/35020086
An intrinsic but cell-nonautonomous defect in GATA-1-overexpressing mouse erythroid cells | Nature
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An intrinsic but cell-nonautonomous defect in GATA-1-overexpressing mouse erythroid cells

Nature volume 406, pages 519–524 (2000)Cite this article

An Erratum to this article was published on 23 November 2000

Abstract

GATA-1 is a tissue-specific transcription factor that is essential for the production of red blood cells1,2. Here we show that overexpression of GATA-1 in erythroid cells inhibits their differentiation, leading to a lethal anaemia. Using chromosome-X-inactivation of a GATA-1 transgene and chimaeric animals, we show that this defect is intrinsic to erythroid cells, but nevertheless cell nonautonomous. Usually, cell nonautonomy is thought to reflect aberrant gene function in cells other than those that exhibit the phenotype3. On the basis of our data, we propose an alternative mechanism in which a signal originating from wild-type erythroid cells restores normal differentiation to cells overexpressing GATA-1 in vivo. The existence of such a signalling mechanism indicates that previous interpretations of cell-nonautonomous defects may be erroneous in some cases and may in fact assign gene function to incorrect cell types.

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Figure 1: GATA-1 overexpression in vivo.
Figure 2: GATA-1 transgene is subject to X-inactivation.
Figure 3: Cells overexpressing GATA-1 contribute to erythroid lineage in adult chimaeric mice.
Figure 4: GATA-1 overexpressing CFU-Es fail to differentiate and undergo apoptosis in vitro.
Figure 5: A simplified model of the erythroblastic island.

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Acknowledgements

We thank R. Bernards for his critical evaluation, discussions and materials contributing to this work. We also thank M. von Lindern, T. Verkerk, V. Lui, R. Delwel, S. Verbakel, G. Zafarana, N. Gillemans, D. Meijer, T. Stijnen, E. Dzierzak, E. Noteboom, R. Kerkhoven, J.-H. Dannenberg, H. te Riele and members of R. Bernards’ laboratory for advice, assistance and materials at various stages of the project. D.W. is supported by a long-term EMBO Fellowship. F.L. is supported by NWO (Netherlands). R.H. is supported by KNAW (Netherlands). NWO (Netherlands) and the EC supported this work.

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Authors and Affiliations

  1. Division of Molecular Carcinogenesis The Netherlands Cancer Institute, Amsterdam , 1066 CX, The Netherlands

    David Whyatt

  2. Department of Cell Biology and Genetics, Erasmus University, Medical Genetics Centre, PO Box 1738, Rotterdam, 3000 DR, The Netherlands

    Fokke Lindeboom, Alar Karis, Rita Ferreira, Eric Milot, Rudi Hendriks, Marella de Bruijn, An Langeveld, Joost Gribnau, Frank Grosveld & Sjaak Philipsen

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Correspondence to Frank Grosveld.

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Whyatt, D., Lindeboom, F., Karis, A. et al. An intrinsic but cell-nonautonomous defect in GATA-1-overexpressing mouse erythroid cells. Nature 406, 519–524 (2000). https://doi.org/10.1038/35020086

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