Homotypic signalling regulates Gata1 activity in the erythroblastic island.
Gata1 is a transcription factor essential for erythropoiesis. Erythroid cells lacking Gata1 undergo apoptosis, while overexpression of Gata1 results in a block in erythroid differentiation. However, erythroid cells overexpressing Gata1 differentiate normally in vivo when in the presence of wild-type cells. We have proposed a model, whereby a signal generated by wild-type cells (red cell differentiation signal; REDS) overcomes the intrinsic defect in Gata1-overexpressing erythroid cells. The simplest interpretation of this model is that wild-type erythroid cells generate REDS. To substantiate this notion, we have exploited a tissue specific Cre/loxP system and the process of X-inactivation to generate mice that overexpress Gata1 in half the erythroid cells and are Gata1 null in the other half. The results show that the cells supplying REDS are erythroid cells. This study demonstrates the importance of intercellular signalling in regulating Gata1 activity and that this homotypic signalling between erythroid cells is crucial to normal differentiation.
Gutiérrez
Laura
L
Erasmus MC, Department of Cell Biology, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Lindeboom
Fokke
F
Langeveld
An
A
Grosveld
Frank
F
Philipsen
Sjaak
S
Whyatt
David
D
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology*; D050981:Erythroid-Specific DNA-Binding Factors; D005260:Female; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor; D005838:Genotype; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006579:Heterozygote; D008099:Liver / Q000196:embryology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008957:Models, Genetic; D009154:Mutation; D009924:Organ Culture Techniques; D010641:Phenotype; D011995:Recombination, Genetic; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D019076:Transgenes
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D014157:Transcription Factors