|ZFIN ID: ZDB-PUB-200216-4|
Deletion of a conserved Gata2 enhancer impairs haemogenic endothelium programming and adult Zebrafish haematopoiesis
Dobrzycki, T., Mahony, C.B., Krecsmarik, M., Koyunlar, C., Rispoli, R., Peulen-Zink, J., Gussinklo, K., Fedlaoui, B., de Pater, E., Patient, R., Monteiro, R.
|Source:||Communications biology 3: 71 (Journal)|
|Registered Authors:||Mahony, Christopher, Monteiro, Rui, Patient, Roger K.|
|PubMed:||32054973 Full text @ Commun Biol|
Dobrzycki, T., Mahony, C.B., Krecsmarik, M., Koyunlar, C., Rispoli, R., Peulen-Zink, J., Gussinklo, K., Fedlaoui, B., de Pater, E., Patient, R., Monteiro, R. (2020) Deletion of a conserved Gata2 enhancer impairs haemogenic endothelium programming and adult Zebrafish haematopoiesis. Communications biology. 3:71.
ABSTRACTGata2 is a key transcription factor required to generate Haematopoietic Stem and Progenitor Cells (HSPCs) from haemogenic endothelium (HE); misexpression of Gata2 leads to haematopoietic disorders. Here we deleted a conserved enhancer (i4 enhancer) driving pan-endothelial expression of the zebrafish gata2a and showed that Gata2a is required for HE programming by regulating expression of runx1 and of the second Gata2 orthologue, gata2b. By 5 days, homozygous gata2aΔi4/Δi4 larvae showed normal numbers of HSPCs, a recovery mediated by Notch signalling driving gata2b and runx1 expression in HE. However, gata2aΔi4/Δi4 adults showed oedema, susceptibility to infections and marrow hypo-cellularity, consistent with bone marrow failure found in GATA2 deficiency syndromes. Thus, gata2a expression driven by the i4 enhancer is required for correct HE programming in embryos and maintenance of steady-state haematopoietic stem cell output in the adult. These enhancer mutants will be useful in exploring further the pathophysiology of GATA2-related deficiencies in vivo.
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