Teleost growth factor independence (gfi) genes differentially regulate successive waves of hematopoiesis

Cooney, J.D., Hildick-Smith, G.J., Shafizadeh, E., McBride, P.F., Carroll, K.J., Anderson, H., Shaw, G.C., Tamplin, O.J., Branco, D.S., Dalton, A.J., Shah, D.I., Wong, C., Gallagher, P.G., Zon, L.I., North, T.E., and Paw, B.H.
Developmental Biology   373(2): 431-441 (Journal)
Registered Authors
North, Trista, Paw, Barry, Shafizadeh, Ebrahim, Shah, Dhvanit I., Shaw, George C., Tamplin, Owen, Zon, Leonard I.
primitive and definitive hematopoiesis, differentiation, lineage commitment
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • Conserved Sequence/genetics
  • DNA-Binding Proteins/chemistry
  • DNA-Binding Proteins/genetics*
  • DNA-Binding Proteins/metabolism
  • Embryo, Nonmammalian/metabolism
  • Epistasis, Genetic
  • Erythropoiesis/genetics
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental*
  • Hematopoiesis/genetics*
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism
  • Hematopoietic System/embryology
  • Hematopoietic System/metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
22960038 Full text @ Dev. Biol.

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 gfi1aa 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 the gfi factors and key hematopoietic transcription factors, demonstrating that gfi1aa 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.

Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes