Journal
DEVELOPMENTAL BIOLOGY
Volume 373, Issue 2, Pages 431-441Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2012.08.015
Keywords
Primitive and definitive hematopoiesis; Differentiation; Lineage commitment
Categories
Funding
- American Heart Association
- American Society of Hematology
- Finnish Sigrid Juselius Foundation
- CAPES
- FAPESP
- Canadian Institutes of Health Research
- Howard Hughes Medical Institute
- March of Dimes Foundation
- National Institutes of Health [R01 DK070838, P01 HL032262, T32 HL07623, K01 DK085217]
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Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification. In mammals, Gfi1a regulates hematopoietic stem cells (HSC), myeloid and lymphoid populations, while its paralog, Gfi1b, regulates HSC, megakaryocyte and erythroid development. In zebrafish, gfi1aa is essential for primitive hematopoiesis; however, little is known about the role of gif1aa in definitive hematopoiesis or about additional gfi factors in zebrafish. Here, we report the isolation and characterization of an additional hematopoietic gfi factor, gfi1b. We show that gfi1aa and gfi1b are expressed in the primitive and definitive sites of hematopoiesis in zebrafish. Our functional analyses demonstrate that gfi1aa and gfi1b have distinct roles in regulating primitive and definitive hematopoietic progenitors, respectively. Loss of gfi1aa silences markers of early primitive progenitors, scl and gata1. Conversely, loss of gfi1b silences runx-1, c-myb, ikaros and cd41, indicating that gfi1b is required for definitive hematopoiesis. We determine the epistatic relationships between thee factors and key hematopoietic transcription factors, demonstrating that gif1aa and gfi1b join lmo2, scl, runx-1 and c-myb as critical regulators of teleost HSPC. Our studies establish a comparative paradigm for the regulation of hematopoietic lineages by gfi transcription factors. (C) 2012 Elsevier Inc. All rights reserved.
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